TY  - JOUR
AU  - Milaković, Dragana
AU  - Kovačević, Tijana
AU  - Kovačević, Peđa
AU  - Barišić, Vedrana
AU  - Avram, Sanja
AU  - Dragić, Saša
AU  - Zlojutro, Biljana
AU  - Momčičević, Danica
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5557
AB  - During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients’ individual PK parameters and corresponding concentration–time profiles using the PopPK model, following the administration of 600 mg/8 h (a higher-than-standard dosing) and 600 mg/12 h (standard). The probabilities of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg/8 h was predicted to achieve greater than or equal to 85%Tf>MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg/L. In addition, for the same MIC, fAUC24/MIC ≥ 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential.
PB  - MDPI
T2  - Pharmaceutics
T1  - Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing
VL  - 16
IS  - 2
DO  - 10.3390/pharmaceutics16020253
ER  - 

@article{
author = "Milaković, Dragana and Kovačević, Tijana and Kovačević, Peđa and Barišić, Vedrana and Avram, Sanja and Dragić, Saša and Zlojutro, Biljana and Momčičević, Danica and Miljković, Branislava and Vučićević, Katarina",
year = "2024",
abstract = "During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients’ individual PK parameters and corresponding concentration–time profiles using the PopPK model, following the administration of 600 mg/8 h (a higher-than-standard dosing) and 600 mg/12 h (standard). The probabilities of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg/8 h was predicted to achieve greater than or equal to 85%Tf>MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg/L. In addition, for the same MIC, fAUC24/MIC ≥ 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing",
volume = "16",
number = "2",
doi = "10.3390/pharmaceutics16020253"
}

Milaković, D., Kovačević, T., Kovačević, P., Barišić, V., Avram, S., Dragić, S., Zlojutro, B., Momčičević, D., Miljković, B.,& Vučićević, K.. (2024). Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing. in Pharmaceutics
MDPI., 16(2).
https://doi.org/10.3390/pharmaceutics16020253

Milaković D, Kovačević T, Kovačević P, Barišić V, Avram S, Dragić S, Zlojutro B, Momčičević D, Miljković B, Vučićević K. Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing. in Pharmaceutics. 2024;16(2).
doi:10.3390/pharmaceutics16020253 .

Milaković, Dragana, Kovačević, Tijana, Kovačević, Peđa, Barišić, Vedrana, Avram, Sanja, Dragić, Saša, Zlojutro, Biljana, Momčičević, Danica, Miljković, Branislava, Vučićević, Katarina, "Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing" in Pharmaceutics, 16, no. 2 (2024),
https://doi.org/10.3390/pharmaceutics16020253 . .

TY  - JOUR
AU  - Škorić, Biljana
AU  - Jovanović, Marija
AU  - Kuzmanović, Miloš
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5583
AB  - Purpose: The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) and to describe the influence of variability factors. Methods: The study included 50 patients of both sexes (aged 1–18 years) who received 3 or 5 g/m2 of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis. Parameter estimation was performed by first-order conditional estimation method with interaction (FOCEI), whereas stepwise covariate modeling was used to assess variability factors. Results: The final model is a two-compartment model that incorporates the effect of body surface area and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical subject were estimated at 5.75 L/h/m2 for clearance (CL), 21.3 L/m2 for volume of the central compartment (V1), 8.2 L/m2 for volume of the peripheral compartment (V2), and 0.087 L/h/m2 for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 32% in MTX CL was observed among patients’ hemoglobin values reported in the study. Conclusion: The developed population pharmacokinetic model can contribute to the therapy optimization during HDMTX in pediatric patients with ALL and NHL. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to the disposition of HDMTX.
PB  - Springer Science and Business Media Deutschland GmbH
T2  - European Journal of Clinical Pharmacology
T1  - Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies
DO  - 10.1007/s00228-024-03642-4
ER  - 

@article{
author = "Škorić, Biljana and Jovanović, Marija and Kuzmanović, Miloš and Miljković, Branislava and Vučićević, Katarina",
year = "2024",
abstract = "Purpose: The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) and to describe the influence of variability factors. Methods: The study included 50 patients of both sexes (aged 1–18 years) who received 3 or 5 g/m2 of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis. Parameter estimation was performed by first-order conditional estimation method with interaction (FOCEI), whereas stepwise covariate modeling was used to assess variability factors. Results: The final model is a two-compartment model that incorporates the effect of body surface area and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical subject were estimated at 5.75 L/h/m2 for clearance (CL), 21.3 L/m2 for volume of the central compartment (V1), 8.2 L/m2 for volume of the peripheral compartment (V2), and 0.087 L/h/m2 for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 32% in MTX CL was observed among patients’ hemoglobin values reported in the study. Conclusion: The developed population pharmacokinetic model can contribute to the therapy optimization during HDMTX in pediatric patients with ALL and NHL. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to the disposition of HDMTX.",
publisher = "Springer Science and Business Media Deutschland GmbH",
journal = "European Journal of Clinical Pharmacology",
title = "Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies",
doi = "10.1007/s00228-024-03642-4"
}

Škorić, B., Jovanović, M., Kuzmanović, M., Miljković, B.,& Vučićević, K.. (2024). Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies. in European Journal of Clinical Pharmacology
Springer Science and Business Media Deutschland GmbH..
https://doi.org/10.1007/s00228-024-03642-4

Škorić B, Jovanović M, Kuzmanović M, Miljković B, Vučićević K. Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies. in European Journal of Clinical Pharmacology. 2024;.
doi:10.1007/s00228-024-03642-4 .

Škorić, Biljana, Jovanović, Marija, Kuzmanović, Miloš, Miljković, Branislava, Vučićević, Katarina, "Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies" in European Journal of Clinical Pharmacology (2024),
https://doi.org/10.1007/s00228-024-03642-4 . .

TY  - CONF
AU  - Vučićević, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5355
AB  - Farmakometrijski modeli predstavljaju moćni alat i neizostavni su aspekt u savremenim
farmaceutskim istraživanjima i kliničkoj praksi. Oni obezbeđuju kvantitativni okvir za razumevanje
složene interakcije između karakteristika leka, pacijenta i bolesti, omogućavajući izbor leka i režima
doziranja radi optimizacije terapijskih ishoda (1). Pacijenti se međusobno razlikuju u odgovoru na
lekove zbog genetskih, fizioloških, kliničkih ili faktora sredine. Različit odgovor na terapiju može biti
farmakokinetičke, farmakodinamičke ili prirode same bolesti, što ukazuje da jedna doza ne odgovara
svim pacijentima. U cilju stratifikacije režima doziranja za specifične populacije pacijenata, rešavanje
varijabilnosti je od suštinskog značaja. Jedna od ključnih prednosti farmakometrijskih modela leži u
njihovoj sposobnosti da razdvoje različite nivoe varijabilnosti u ponašanju leka, a posebno u
kvantifikaciji i matematičkom opisivanju izvora interindividualne varijabilnosti, kao i predviđanju
kako će različiti pacijenti reagovati na lek. Upravo su ova znanja od neprocenjive vrednosti za
specifične populacije pacijenata kako bi se identifikovali optimalni režimi doziranja koji obezbeđuju
maksimalnu efikasnost uz minimalne neželjene efekte terapije. Farmakometrijskim-modelima
vođeno doziranje je značajno kod pedijatrijskih, starijih, kritično-obolelih ili pacijenata sa
oslabljenom funkcijom jetre/bubrega, gde preporuka o jedinstvenom režimu doziranja za sve
pacijente često nije primenljiva u kliničkoj praksi (2). U okviru predavanja će biti prikazani rezultati
istraživanja gde farmakometrijski modeli doprinose novim saznanjima i unapređuju razvoj lekova
otključavanjem potencijala personalizovane medicine.
AB  - Pharmacometric models are a powerful tool and an essential aspect of modern pharmaceutical
research, drug development and clinical practice. They provide a quantitative framework for
understanding the complex interaction between drug characteristics, patients, and diseases, enabling
the selection of drugs and dosing regimens to optimize therapeutic outcomes (1). Patients vary in
their response to medications due to genetic, physiological, clinical, or environmental factors.
Different responses to therapy can be of pharmacokinetic, pharmacodynamic, or disease-related
nature, indicating that one dose does not fit all patients. Addressing the variability is essential for
stratifying dosing regimens for specific patient populations. One of the key advantages of
pharmacometric models lies in their ability to distinguish different levels of variability in drug
behavior, especially in quantifying and mathematically describing the sources of interindividual
variability, as well as predicting how different patients will react to the drug. This knowledge is
invaluable for specific patient populations to identify optimal dosing regimens that provide
maximum efficacy with minimal side effects. Model-informed dosing is significant in pediatrics,
elderly, critically ill patients, or patients with impaired liver/kidney function, where a one-size-fits-
all dosing recommendation is often not applicable (2). The lecture will present research results where
pharmacometric models contribute to new insights and improve drug development by unlocking the
potential of personalized medicine.
PB  - Savez farmaceutskih udruženja Srbije
C3  - Arhiv za farmaciju
T1  - Farmakometrijski modeli – savremen alat za kvantifikaciju varijabilnosti i individualizaciju režima doziranja lekova
T1  - Pharmacometric models - a modern tool for quantifying variability and individualizing drug dosing regimens
VL  - 73
IS  - Suppl. 4
SP  - S11
EP  - S12
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5355
ER  - 

@conference{
author = "Vučićević, Katarina",
year = "2023",
abstract = "Farmakometrijski modeli predstavljaju moćni alat i neizostavni su aspekt u savremenim
farmaceutskim istraživanjima i kliničkoj praksi. Oni obezbeđuju kvantitativni okvir za razumevanje
složene interakcije između karakteristika leka, pacijenta i bolesti, omogućavajući izbor leka i režima
doziranja radi optimizacije terapijskih ishoda (1). Pacijenti se međusobno razlikuju u odgovoru na
lekove zbog genetskih, fizioloških, kliničkih ili faktora sredine. Različit odgovor na terapiju može biti
farmakokinetičke, farmakodinamičke ili prirode same bolesti, što ukazuje da jedna doza ne odgovara
svim pacijentima. U cilju stratifikacije režima doziranja za specifične populacije pacijenata, rešavanje
varijabilnosti je od suštinskog značaja. Jedna od ključnih prednosti farmakometrijskih modela leži u
njihovoj sposobnosti da razdvoje različite nivoe varijabilnosti u ponašanju leka, a posebno u
kvantifikaciji i matematičkom opisivanju izvora interindividualne varijabilnosti, kao i predviđanju
kako će različiti pacijenti reagovati na lek. Upravo su ova znanja od neprocenjive vrednosti za
specifične populacije pacijenata kako bi se identifikovali optimalni režimi doziranja koji obezbeđuju
maksimalnu efikasnost uz minimalne neželjene efekte terapije. Farmakometrijskim-modelima
vođeno doziranje je značajno kod pedijatrijskih, starijih, kritično-obolelih ili pacijenata sa
oslabljenom funkcijom jetre/bubrega, gde preporuka o jedinstvenom režimu doziranja za sve
pacijente često nije primenljiva u kliničkoj praksi (2). U okviru predavanja će biti prikazani rezultati
istraživanja gde farmakometrijski modeli doprinose novim saznanjima i unapređuju razvoj lekova
otključavanjem potencijala personalizovane medicine., Pharmacometric models are a powerful tool and an essential aspect of modern pharmaceutical
research, drug development and clinical practice. They provide a quantitative framework for
understanding the complex interaction between drug characteristics, patients, and diseases, enabling
the selection of drugs and dosing regimens to optimize therapeutic outcomes (1). Patients vary in
their response to medications due to genetic, physiological, clinical, or environmental factors.
Different responses to therapy can be of pharmacokinetic, pharmacodynamic, or disease-related
nature, indicating that one dose does not fit all patients. Addressing the variability is essential for
stratifying dosing regimens for specific patient populations. One of the key advantages of
pharmacometric models lies in their ability to distinguish different levels of variability in drug
behavior, especially in quantifying and mathematically describing the sources of interindividual
variability, as well as predicting how different patients will react to the drug. This knowledge is
invaluable for specific patient populations to identify optimal dosing regimens that provide
maximum efficacy with minimal side effects. Model-informed dosing is significant in pediatrics,
elderly, critically ill patients, or patients with impaired liver/kidney function, where a one-size-fits-
all dosing recommendation is often not applicable (2). The lecture will present research results where
pharmacometric models contribute to new insights and improve drug development by unlocking the
potential of personalized medicine.",
publisher = "Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Farmakometrijski modeli – savremen alat za kvantifikaciju varijabilnosti i individualizaciju režima doziranja lekova, Pharmacometric models - a modern tool for quantifying variability and individualizing drug dosing regimens",
volume = "73",
number = "Suppl. 4",
pages = "S11-S12",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5355"
}

Vučićević, K.. (2023). Farmakometrijski modeli – savremen alat za kvantifikaciju varijabilnosti i individualizaciju režima doziranja lekova. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije., 73(Suppl. 4), S11-S12.
https://hdl.handle.net/21.15107/rcub_farfar_5355

Vučićević K. Farmakometrijski modeli – savremen alat za kvantifikaciju varijabilnosti i individualizaciju režima doziranja lekova. in Arhiv za farmaciju. 2023;73(Suppl. 4):S11-S12.
https://hdl.handle.net/21.15107/rcub_farfar_5355 .

Vučićević, Katarina, "Farmakometrijski modeli – savremen alat za kvantifikaciju varijabilnosti i individualizaciju režima doziranja lekova" in Arhiv za farmaciju, 73, no. Suppl. 4 (2023):S11-S12,
https://hdl.handle.net/21.15107/rcub_farfar_5355 .

TY  - JOUR
AU  - Homšek, Ana
AU  - Spasić, Jelena
AU  - Nikolić, Neda
AU  - Stanojković, Tatjana
AU  - Jovanović, Marija
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4325
AB  - Objective: Therapeutic monoclonal antibodies in oncology are slowly becoming the dominant treatment option for many different cancer types. The main route of administration, infusion, requires extensive product preparations, patient hospitalization and close monitoring. Patient comfort improvement, staff workload reduction and cost savings dictated the development of subcutaneous formulations. The aim of this review is to present pharmacokinetic characteristics of subcutaneous products, discuss the differences between intravenous and subcutaneous routes and to point out the advantages as well as challenges of administration route shift from the formulation development and pharmacometric angle. Data sources: Food and Drug administration's Purple book database and electronic medicines compendium were used to identify monoclonal antibodies in oncology approved as subcutaneous forms. Using keywords subcutaneous, monoclonal antibodies, pharmacokinetics, model, as well as specific drugs previously identified, both PubMed and ScienceDirect databases were researched. Data summary: There are currently six approved subcutaneous onco-monoclonal antibodies on the market. For each of them, exposure to the drug was similar in relation to infusion, treatment effectiveness was the same, administration was well tolerated by the patients and costs of the medical service were reduced. Conclusion: Development of subcutaneous forms for existing and emerging new monoclonal antibodies for cancer treatment as well as shifting from administration via infusion should be encouraged due to patient preference, lower costs and overall lack of substantial differences in efficacy and safety between the two routes.
PB  - SAGE Publications Ltd
T2  - Journal of Oncology Pharmacy Practice
T1  - Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology
VL  - 29
IS  - 2
SP  - 431
EP  - 440
DO  - 10.1177/10781552221137702
ER  - 

@article{
author = "Homšek, Ana and Spasić, Jelena and Nikolić, Neda and Stanojković, Tatjana and Jovanović, Marija and Miljković, Branislava and Vučićević, Katarina",
year = "2023",
abstract = "Objective: Therapeutic monoclonal antibodies in oncology are slowly becoming the dominant treatment option for many different cancer types. The main route of administration, infusion, requires extensive product preparations, patient hospitalization and close monitoring. Patient comfort improvement, staff workload reduction and cost savings dictated the development of subcutaneous formulations. The aim of this review is to present pharmacokinetic characteristics of subcutaneous products, discuss the differences between intravenous and subcutaneous routes and to point out the advantages as well as challenges of administration route shift from the formulation development and pharmacometric angle. Data sources: Food and Drug administration's Purple book database and electronic medicines compendium were used to identify monoclonal antibodies in oncology approved as subcutaneous forms. Using keywords subcutaneous, monoclonal antibodies, pharmacokinetics, model, as well as specific drugs previously identified, both PubMed and ScienceDirect databases were researched. Data summary: There are currently six approved subcutaneous onco-monoclonal antibodies on the market. For each of them, exposure to the drug was similar in relation to infusion, treatment effectiveness was the same, administration was well tolerated by the patients and costs of the medical service were reduced. Conclusion: Development of subcutaneous forms for existing and emerging new monoclonal antibodies for cancer treatment as well as shifting from administration via infusion should be encouraged due to patient preference, lower costs and overall lack of substantial differences in efficacy and safety between the two routes.",
publisher = "SAGE Publications Ltd",
journal = "Journal of Oncology Pharmacy Practice",
title = "Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology",
volume = "29",
number = "2",
pages = "431-440",
doi = "10.1177/10781552221137702"
}

Homšek, A., Spasić, J., Nikolić, N., Stanojković, T., Jovanović, M., Miljković, B.,& Vučićević, K.. (2023). Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology. in Journal of Oncology Pharmacy Practice
SAGE Publications Ltd., 29(2), 431-440.
https://doi.org/10.1177/10781552221137702

Homšek A, Spasić J, Nikolić N, Stanojković T, Jovanović M, Miljković B, Vučićević K. Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology. in Journal of Oncology Pharmacy Practice. 2023;29(2):431-440.
doi:10.1177/10781552221137702 .

Homšek, Ana, Spasić, Jelena, Nikolić, Neda, Stanojković, Tatjana, Jovanović, Marija, Miljković, Branislava, Vučićević, Katarina, "Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology" in Journal of Oncology Pharmacy Practice, 29, no. 2 (2023):431-440,
https://doi.org/10.1177/10781552221137702 . .

TY  - JOUR
AU  - Panić, Bojana
AU  - Jovanović, Marija
AU  - Lukić, Vera
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
AU  - Milovanović, Srđan
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5040
AB  - Purpose: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. Methods: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. Results: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. Conclusion: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant.
PB  - Springer
T2  - European Journal of Clinical Pharmacology
T1  - Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid
DO  - 10.1007/s00228-023-03569-2
ER  - 

@article{
author = "Panić, Bojana and Jovanović, Marija and Lukić, Vera and Vučićević, Katarina and Miljković, Branislava and Milovanović, Srđan",
year = "2023",
abstract = "Purpose: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. Methods: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. Results: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. Conclusion: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant.",
publisher = "Springer",
journal = "European Journal of Clinical Pharmacology",
title = "Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid",
doi = "10.1007/s00228-023-03569-2"
}

Panić, B., Jovanović, M., Lukić, V., Vučićević, K., Miljković, B.,& Milovanović, S.. (2023). Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid. in European Journal of Clinical Pharmacology
Springer..
https://doi.org/10.1007/s00228-023-03569-2

Panić B, Jovanović M, Lukić V, Vučićević K, Miljković B, Milovanović S. Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid. in European Journal of Clinical Pharmacology. 2023;.
doi:10.1007/s00228-023-03569-2 .

Panić, Bojana, Jovanović, Marija, Lukić, Vera, Vučićević, Katarina, Miljković, Branislava, Milovanović, Srđan, "Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid" in European Journal of Clinical Pharmacology (2023),
https://doi.org/10.1007/s00228-023-03569-2 . .

TY  - JOUR
AU  - Jovanović, Marija
AU  - Kovačević, Milena
AU  - Catić-Đorđević, Aleksandra
AU  - Ćulafić, Milica
AU  - Stefanović, Nikola
AU  - Mitić, Branka
AU  - Vučićević, Katarina
AU  - Vezmar-Kovačević, Sandra
AU  - Veličković-Radovanović, Radmila
AU  - Miljković, Branislava
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4921
AB  - The study aimed to estimate and compare the prevalence and type of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) between the STOPP/START original (v1) and updated version (v2) among older patients in various settings, as well as associated factors. The study included 440 patients attending a community pharmacy, 200 outpatients and 140 nursing home users. An increase in the prevalence of STOPP v2 (57.9%) compared to v1 (56.2%) was not statistically significant in the total sample and within each setting (p>0.05). A decrease in the prevalence of START v1 (55.8%) to v2 (41.2%) was statistically significant (p<0.001) in the total sample and within each setting (p<0.05). Drug indication (32.9%) and fall-risk medications (32.2%) were most commonly identified for STOPP v2, while cardiovascular system criteria (30.5%) were the most frequently detected for START v2. The number of medications was the strongest predictor for both STOPP v1 and v2, with odds ratio values of 1.35 and 1.34, respectively. Patients’ characteristics associated with the occurrence of STOPP and START criteria were identified. According to both STOPP/START versions, the results indicate a substantial rate of potentially inappropriate prescribing among elderly patients. The prevalence of PIMs was slightly higher with the updated version, while the prevalence of PPOs was significantly lower.
T2  - Brazilian Journal of Pharmaceutical Sciences
T1  - Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria
VL  - 59
DO  - 10.1590/s2175-97902023e22549
ER  - 

@article{
author = "Jovanović, Marija and Kovačević, Milena and Catić-Đorđević, Aleksandra and Ćulafić, Milica and Stefanović, Nikola and Mitić, Branka and Vučićević, Katarina and Vezmar-Kovačević, Sandra and Veličković-Radovanović, Radmila and Miljković, Branislava",
year = "2023",
abstract = "The study aimed to estimate and compare the prevalence and type of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) between the STOPP/START original (v1) and updated version (v2) among older patients in various settings, as well as associated factors. The study included 440 patients attending a community pharmacy, 200 outpatients and 140 nursing home users. An increase in the prevalence of STOPP v2 (57.9%) compared to v1 (56.2%) was not statistically significant in the total sample and within each setting (p>0.05). A decrease in the prevalence of START v1 (55.8%) to v2 (41.2%) was statistically significant (p<0.001) in the total sample and within each setting (p<0.05). Drug indication (32.9%) and fall-risk medications (32.2%) were most commonly identified for STOPP v2, while cardiovascular system criteria (30.5%) were the most frequently detected for START v2. The number of medications was the strongest predictor for both STOPP v1 and v2, with odds ratio values of 1.35 and 1.34, respectively. Patients’ characteristics associated with the occurrence of STOPP and START criteria were identified. According to both STOPP/START versions, the results indicate a substantial rate of potentially inappropriate prescribing among elderly patients. The prevalence of PIMs was slightly higher with the updated version, while the prevalence of PPOs was significantly lower.",
journal = "Brazilian Journal of Pharmaceutical Sciences",
title = "Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria",
volume = "59",
doi = "10.1590/s2175-97902023e22549"
}

Jovanović, M., Kovačević, M., Catić-Đorđević, A., Ćulafić, M., Stefanović, N., Mitić, B., Vučićević, K., Vezmar-Kovačević, S., Veličković-Radovanović, R.,& Miljković, B.. (2023). Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria. in Brazilian Journal of Pharmaceutical Sciences, 59.
https://doi.org/10.1590/s2175-97902023e22549

Jovanović M, Kovačević M, Catić-Đorđević A, Ćulafić M, Stefanović N, Mitić B, Vučićević K, Vezmar-Kovačević S, Veličković-Radovanović R, Miljković B. Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria. in Brazilian Journal of Pharmaceutical Sciences. 2023;59.
doi:10.1590/s2175-97902023e22549 .

Jovanović, Marija, Kovačević, Milena, Catić-Đorđević, Aleksandra, Ćulafić, Milica, Stefanović, Nikola, Mitić, Branka, Vučićević, Katarina, Vezmar-Kovačević, Sandra, Veličković-Radovanović, Radmila, Miljković, Branislava, "Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria" in Brazilian Journal of Pharmaceutical Sciences, 59 (2023),
https://doi.org/10.1590/s2175-97902023e22549 . .

TY  - JOUR
AU  - Jovanović, Marija
AU  - Kovačević, Milena
AU  - Vezmar-Kovačević, Sandra
AU  - Palibrk, Ivan
AU  - Bjelanović, Jasna
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4378
AB  - Background: The study aimed to estimate lidocaine (LID)
pharmacokinetic parameter values in patients with
impaired liver function, level of correlation between the
pharmacokinetic parameters and Child-Pugh class and
change in pharmacokinetic parameters after liver tumor
resection compared to the preoperative value.
Methods: Patients with impaired liver function were subject
to the LID test 1 day prior to, 3 and 7 days after the inter-
vention. LID was administered in single i.v. dose of 1 mg/kg.
Blood samples were collected at 15, 30 and 90 minutes
after drug administration. Non-compartmental analysis was
applied for calculating the pharmacokinetic parameters.
Results: The study included 17 patients with the diagnosis of
cirrhosis and 41 patients with liver tumor. In both groups of
patients, the values of the coefficients of correlation show
the best correlation between clearance (CL) and Child-Pugh
score (-0.693, p<0.005) over other pharmacokinetic
parameters. The results indicate worsening hepatic function
on 3rd day after operation in comparison to the values of
LID CL prior to operation (mean LID CL for patients with
Child-Pugh class A are 25.91 L/h, 41.59 L/h, respectively;
while for B class are 16.89 L/h, 22.65 L/h, respectively). On
day 7th, the values of LID CL (mean value for patients with
Child-Pugh class A and B are 40.98 L/h and 21.46 L/h,
respectively) are increased in comparison to 3rd day after.
Conclusions: LID pharmacokinetic parameters consequent-
ly changed according to the severity of liver impairment,
assessed by Child-Pugh score. Values of LID CL and vol-
ume of distribution (Vd) coupled with standard biochemical
parameters may be used for preoperative assessment of
liver function and monitoring of its postoperative recovery.
AB  - Uvod: Cilj studije bila je procena vrednosti farmako-
kinetičkih parametara lidokaina (LID) kod pacijenata sa
oštećenom funkcijom jetre, stepena korelacije izme|u
farmakokinetičkih parametara i Child-Pugh klase i promene farmakokinetičkih parametara posle resekcije tumora
jetre u odnosu na preoperativnu vrednost.
Metode: Pacijenti sa o{te}enom funkcijom jetre bili su
podvrgnuti LID testu 1 dan pre, 3. i 7. dana nakon
intervencije. LID je primenjen u pojedinačnoj i.v. dozi od 1
mg/kg. Uzorci krvi su sakupljeni 15, 30 i 90 minuta nakon
primene leka. Za izračunavanje farmakokinetičkih
parametara primenjena je neprostorna analiza.
Rezultati: Studijom je obuhvaćeno 17 pacijenata sa
dijagnozom ciroze i 41 pacijent sa tumorom jetre. Kod obe
grupe pacijenata, vrednosti koeficijenata korelacije
pokazuju najbolju korelaciju izme|u klirensa LID (CL) i
Child-Pugh skora (-0,693, p<0,005) u odnosu na ostale
farmakokinetičke parametre. Rezultati ukazuju na pogoršanje funkcije jetre 3. dana nakon operacije u pore|enju sa
vrednostima LID CL pre operacije (srednje vrednosti LID CL
kod pacijenata Child-Pugh grupe A iznosile su 25,91 L/h,
41,59 L/h, respektivno; dok su kod pacijenata u klasi B
iznosile 16,89 L/h, 22,65 L/h, respektivno). Sedmog dana
vrednosti LID CL (srednja vrednost u Child-Pugh grupi A i B
iznosile su 40,98 L/h i 21,46 L/h, respektivno) bile su veće
u odnosu na 3. dan posle hirur{ke intervencije.
Zaključak: Farmakokinetički parametri LID se razlikuju u
zavisnosti od težine oštećenja jetre, procenjenih Child-Pugh
skorom. Vrednosti farmakokinetičkih parametara LID u
kombinaciji sa standardnim biohemijskim parametrima
mogu se koristiti za preoperativnu procenu funkcije jetre i
praćenje njenog postoperativnog oporavka
PB  - Beograd : Društvo medicinskih biohemičara Srbije
T2  - Journal of Medical Biochemistry
T1  - Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver
T1  - Klirens lidokaina kao farmakokinetički parametar metaboličke aktivnosti kod pacijenata sa oštećenjem jetre
VL  - 42
SP  - 1
EP  - 7
DO  - 10.5937/jomb0-38952
ER  - 

@article{
author = "Jovanović, Marija and Kovačević, Milena and Vezmar-Kovačević, Sandra and Palibrk, Ivan and Bjelanović, Jasna and Miljković, Branislava and Vučićević, Katarina",
year = "2023",
abstract = "Background: The study aimed to estimate lidocaine (LID)
pharmacokinetic parameter values in patients with
impaired liver function, level of correlation between the
pharmacokinetic parameters and Child-Pugh class and
change in pharmacokinetic parameters after liver tumor
resection compared to the preoperative value.
Methods: Patients with impaired liver function were subject
to the LID test 1 day prior to, 3 and 7 days after the inter-
vention. LID was administered in single i.v. dose of 1 mg/kg.
Blood samples were collected at 15, 30 and 90 minutes
after drug administration. Non-compartmental analysis was
applied for calculating the pharmacokinetic parameters.
Results: The study included 17 patients with the diagnosis of
cirrhosis and 41 patients with liver tumor. In both groups of
patients, the values of the coefficients of correlation show
the best correlation between clearance (CL) and Child-Pugh
score (-0.693, p<0.005) over other pharmacokinetic
parameters. The results indicate worsening hepatic function
on 3rd day after operation in comparison to the values of
LID CL prior to operation (mean LID CL for patients with
Child-Pugh class A are 25.91 L/h, 41.59 L/h, respectively;
while for B class are 16.89 L/h, 22.65 L/h, respectively). On
day 7th, the values of LID CL (mean value for patients with
Child-Pugh class A and B are 40.98 L/h and 21.46 L/h,
respectively) are increased in comparison to 3rd day after.
Conclusions: LID pharmacokinetic parameters consequent-
ly changed according to the severity of liver impairment,
assessed by Child-Pugh score. Values of LID CL and vol-
ume of distribution (Vd) coupled with standard biochemical
parameters may be used for preoperative assessment of
liver function and monitoring of its postoperative recovery., Uvod: Cilj studije bila je procena vrednosti farmako-
kinetičkih parametara lidokaina (LID) kod pacijenata sa
oštećenom funkcijom jetre, stepena korelacije izme|u
farmakokinetičkih parametara i Child-Pugh klase i promene farmakokinetičkih parametara posle resekcije tumora
jetre u odnosu na preoperativnu vrednost.
Metode: Pacijenti sa o{te}enom funkcijom jetre bili su
podvrgnuti LID testu 1 dan pre, 3. i 7. dana nakon
intervencije. LID je primenjen u pojedinačnoj i.v. dozi od 1
mg/kg. Uzorci krvi su sakupljeni 15, 30 i 90 minuta nakon
primene leka. Za izračunavanje farmakokinetičkih
parametara primenjena je neprostorna analiza.
Rezultati: Studijom je obuhvaćeno 17 pacijenata sa
dijagnozom ciroze i 41 pacijent sa tumorom jetre. Kod obe
grupe pacijenata, vrednosti koeficijenata korelacije
pokazuju najbolju korelaciju izme|u klirensa LID (CL) i
Child-Pugh skora (-0,693, p<0,005) u odnosu na ostale
farmakokinetičke parametre. Rezultati ukazuju na pogoršanje funkcije jetre 3. dana nakon operacije u pore|enju sa
vrednostima LID CL pre operacije (srednje vrednosti LID CL
kod pacijenata Child-Pugh grupe A iznosile su 25,91 L/h,
41,59 L/h, respektivno; dok su kod pacijenata u klasi B
iznosile 16,89 L/h, 22,65 L/h, respektivno). Sedmog dana
vrednosti LID CL (srednja vrednost u Child-Pugh grupi A i B
iznosile su 40,98 L/h i 21,46 L/h, respektivno) bile su veće
u odnosu na 3. dan posle hirur{ke intervencije.
Zaključak: Farmakokinetički parametri LID se razlikuju u
zavisnosti od težine oštećenja jetre, procenjenih Child-Pugh
skorom. Vrednosti farmakokinetičkih parametara LID u
kombinaciji sa standardnim biohemijskim parametrima
mogu se koristiti za preoperativnu procenu funkcije jetre i
praćenje njenog postoperativnog oporavka",
publisher = "Beograd : Društvo medicinskih biohemičara Srbije",
journal = "Journal of Medical Biochemistry",
title = "Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver, Klirens lidokaina kao farmakokinetički parametar metaboličke aktivnosti kod pacijenata sa oštećenjem jetre",
volume = "42",
pages = "1-7",
doi = "10.5937/jomb0-38952"
}

Jovanović, M., Kovačević, M., Vezmar-Kovačević, S., Palibrk, I., Bjelanović, J., Miljković, B.,& Vučićević, K.. (2023). Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver. in Journal of Medical Biochemistry
Beograd : Društvo medicinskih biohemičara Srbije., 42, 1-7.
https://doi.org/10.5937/jomb0-38952

Jovanović M, Kovačević M, Vezmar-Kovačević S, Palibrk I, Bjelanović J, Miljković B, Vučićević K. Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver. in Journal of Medical Biochemistry. 2023;42:1-7.
doi:10.5937/jomb0-38952 .

Jovanović, Marija, Kovačević, Milena, Vezmar-Kovačević, Sandra, Palibrk, Ivan, Bjelanović, Jasna, Miljković, Branislava, Vučićević, Katarina, "Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver" in Journal of Medical Biochemistry, 42 (2023):1-7,
https://doi.org/10.5937/jomb0-38952 . .

TY  - CONF
AU  - Roganović, Maša
AU  - Stanojković, Tatjana
AU  - Nikitović, Marina
AU  - Petrović, Nina
AU  - Đurić, Ana
AU  - Matić, Ivana
AU  - Jovanović, Marija
AU  - Vučićević, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4899
AB  - Introduction: The second most common form of cancer in the male population is prostate cancer. Therapeutic options include radical prostatectomy, different forms of radiotherapy, hormone treatment and chemotherapy. Radical prostatectomy and radiotherapy are the most frequently used strategies and enable a long survival for patients diagnosed on time. Because of the prostate anatomy, patients that are on radiotherapy experience a great range of side effects, and even after the therapy is finished, side effects such as urogenital and gastrointestinal toxicity can persist for years. Although survival is long regardless of the therapeutic option used, choosing the appropriate therapeutic options for the patients in terms of efficacy and safety is very important [1]. 

Objectives: We aimed in developing a model for repeated count data, i.e. fatigue, which is the most common adverse event that patients experience during radiotherapy. In addition, the objective of the study is to assess the effect of various covariates on the probability of the event happening using different modelling approaches [2]. 

Methods: Data collected from prostate cancer patients included: age, concentrations of glutamine and glutamate before radiotherapy and after 5, 15, 25 and 30 fractions of radiotherapy, as well as a month after the last fraction of radiotherapy (first follow – up visit), genetic testing results regarding variants in glutamine metabolic pathway, signs and symptoms of acute or chronic urogenital and gastrointestinal toxicity, fatigue, details of their treatment (e.g. radical prostatectomy, hormone therapy), their smoking and alcohol intake status, presence of hypertension or diabetes mellitus type II, and other laboratory findings of significance. Analysis was performed using nonlinear mixed effects modelling approach using NONMEM® software (version 7.4). We tested two approaches: modelling using the first-order estimation method and the Laplace method of estimation in order to create a Poisson model for count data. NONMEM outputs were handled in R software (graphical diagnostics). Model evaluation has been performed using numerical and visual approaches. Covariate model building was performed using a stepwise covariate procedure (SCM). Covariates that were tested are age, glutamine/glutamate concentrations (continuous, time-varying covariates). The influence of categorical covariates was also examined (smoking and alcohol intake, presence of aforementioned comorbidities). 

Results: In total, we analysed 143 data records from 28 male patients aged 53-82 years (mean±sd: 72.67±6.64), mainly older people (>65 years old) that were included in the analysis. The probability of fatigue occurrence was 78.3%, which was rather high but expected. The objective function value of the developed base model using the Laplace method of estimation was 546.346. The average number of fatigue events occurring in the period from the start of the radiotherapy until the first follow-up visit was estimated to be 2.48 with a 95% confidence interval of 1.655 - 3.305 and RSE of 17%. Interindividual variability in the number of fatigue events per patient was estimated at 48.3%, with a shrinkage of 11.1%. The inclusion of the covariates in the base model did not improve the model fit, so they were not kept in the model. 

Conclusion: Our results confirm that fatigue is one of the most common side effects of radiotherapy. Although our model did not show that examined covariates have an effect on the average number of fatigue events,  further analysis will aim at testing different modelling approaches when it comes to modelling side effects of radiotherapy in order to minimize them in cancer patients. 



[1] Retrieved from https://www.nhs.uk/conditions/prostate-cancer/treatment/ . Last access: 19.3.2023.
[2] Plan E.L. Modeling and simulation of count data.  CPT Pharmacometrics Syst. Pharmacol. 2014: 3 (8): p. e129.
C3  - Page. Abstracts of the Annual Meeting of the Population Approach Group in Europe
T1  - Modelling fatigue events in prostate cancer patients on radiotherapy
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4899
ER  - 

@conference{
author = "Roganović, Maša and Stanojković, Tatjana and Nikitović, Marina and Petrović, Nina and Đurić, Ana and Matić, Ivana and Jovanović, Marija and Vučićević, Katarina",
year = "2023",
abstract = "Introduction: The second most common form of cancer in the male population is prostate cancer. Therapeutic options include radical prostatectomy, different forms of radiotherapy, hormone treatment and chemotherapy. Radical prostatectomy and radiotherapy are the most frequently used strategies and enable a long survival for patients diagnosed on time. Because of the prostate anatomy, patients that are on radiotherapy experience a great range of side effects, and even after the therapy is finished, side effects such as urogenital and gastrointestinal toxicity can persist for years. Although survival is long regardless of the therapeutic option used, choosing the appropriate therapeutic options for the patients in terms of efficacy and safety is very important [1]. 

Objectives: We aimed in developing a model for repeated count data, i.e. fatigue, which is the most common adverse event that patients experience during radiotherapy. In addition, the objective of the study is to assess the effect of various covariates on the probability of the event happening using different modelling approaches [2]. 

Methods: Data collected from prostate cancer patients included: age, concentrations of glutamine and glutamate before radiotherapy and after 5, 15, 25 and 30 fractions of radiotherapy, as well as a month after the last fraction of radiotherapy (first follow – up visit), genetic testing results regarding variants in glutamine metabolic pathway, signs and symptoms of acute or chronic urogenital and gastrointestinal toxicity, fatigue, details of their treatment (e.g. radical prostatectomy, hormone therapy), their smoking and alcohol intake status, presence of hypertension or diabetes mellitus type II, and other laboratory findings of significance. Analysis was performed using nonlinear mixed effects modelling approach using NONMEM® software (version 7.4). We tested two approaches: modelling using the first-order estimation method and the Laplace method of estimation in order to create a Poisson model for count data. NONMEM outputs were handled in R software (graphical diagnostics). Model evaluation has been performed using numerical and visual approaches. Covariate model building was performed using a stepwise covariate procedure (SCM). Covariates that were tested are age, glutamine/glutamate concentrations (continuous, time-varying covariates). The influence of categorical covariates was also examined (smoking and alcohol intake, presence of aforementioned comorbidities). 

Results: In total, we analysed 143 data records from 28 male patients aged 53-82 years (mean±sd: 72.67±6.64), mainly older people (>65 years old) that were included in the analysis. The probability of fatigue occurrence was 78.3%, which was rather high but expected. The objective function value of the developed base model using the Laplace method of estimation was 546.346. The average number of fatigue events occurring in the period from the start of the radiotherapy until the first follow-up visit was estimated to be 2.48 with a 95% confidence interval of 1.655 - 3.305 and RSE of 17%. Interindividual variability in the number of fatigue events per patient was estimated at 48.3%, with a shrinkage of 11.1%. The inclusion of the covariates in the base model did not improve the model fit, so they were not kept in the model. 

Conclusion: Our results confirm that fatigue is one of the most common side effects of radiotherapy. Although our model did not show that examined covariates have an effect on the average number of fatigue events,  further analysis will aim at testing different modelling approaches when it comes to modelling side effects of radiotherapy in order to minimize them in cancer patients. 



[1] Retrieved from https://www.nhs.uk/conditions/prostate-cancer/treatment/ . Last access: 19.3.2023.
[2] Plan E.L. Modeling and simulation of count data.  CPT Pharmacometrics Syst. Pharmacol. 2014: 3 (8): p. e129.",
journal = "Page. Abstracts of the Annual Meeting of the Population Approach Group in Europe",
title = "Modelling fatigue events in prostate cancer patients on radiotherapy",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4899"
}

Roganović, M., Stanojković, T., Nikitović, M., Petrović, N., Đurić, A., Matić, I., Jovanović, M.,& Vučićević, K.. (2023). Modelling fatigue events in prostate cancer patients on radiotherapy. in Page. Abstracts of the Annual Meeting of the Population Approach Group in Europe.
https://hdl.handle.net/21.15107/rcub_farfar_4899

Roganović M, Stanojković T, Nikitović M, Petrović N, Đurić A, Matić I, Jovanović M, Vučićević K. Modelling fatigue events in prostate cancer patients on radiotherapy. in Page. Abstracts of the Annual Meeting of the Population Approach Group in Europe. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_4899 .

Roganović, Maša, Stanojković, Tatjana, Nikitović, Marina, Petrović, Nina, Đurić, Ana, Matić, Ivana, Jovanović, Marija, Vučićević, Katarina, "Modelling fatigue events in prostate cancer patients on radiotherapy" in Page. Abstracts of the Annual Meeting of the Population Approach Group in Europe (2023),
https://hdl.handle.net/21.15107/rcub_farfar_4899 .

TY  - CONF
AU  - Homšek, Ana
AU  - Marković, Srđan
AU  - Kralj, Đorđe
AU  - Odanović, Olga
AU  - Svorcan, Petar
AU  - Jovanović, Marija
AU  - Vučićević, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4898
AB  - Introduction: Infliximab (IFX), anti-tumour necrosis factor alpha antibody, is widely used in the treatment of inflammatory bowel diseases. Patients with Crohn’s disease may develop a more complicated form which involves fistulae formation, most commonly perianal. IFX has been effective in inducing fistula closure and maintaining disease remission [1]. In order to achieve fistulae healing adequate trough concentrations should be achieved [2].

Objectives:

Obtaining PK parameters for patients with the fistulising disease form
Comparing the results to the ones available in the literature for Crohn’s disease
Methods: In a retrospective review of medical documentation (from 2013 to present), 42 patients (64% male, 18-65 years old) with fistulising Crohn’s disease were selected for analysis. IFX concentrations were measured just before dose administration (trough concentration) or earlier if the patient was experiencing severe disease symptoms. For the majority of patients concentration was measured at week 14, right before the first maintenance dose. Additional concentrations were obtained at scheduled check-ups or after patients experienced signs of relapse. After appropriate premedication, each patient received the calculated fixed dose based on their body weight (dose range was 200-800 mg) via two-hour infusion. The drug was administered according to the standard (week 0, 2 and 6) and accelerated induction (every two weeks) protocols, followed by maintenance therapy (every 4, 6 or 8 weeks). Population modelling approach was applied to characterize pharmacokinetic profile of IFX using NONMEM 7.3 software (ICON Development Solutions Inc., Dublin, Ireland) [3]. The obtained data were processed using Microsoft Excel and R software.

Results: After exclusion of concentrations over the upper limit of quantification (12 μg/mL), a total of 161 concentrations were analysed. IFX concentrations below lower limit of quantification were accounted for using the M5 method [4]. Pharmacokinetics of IFX has, so far, been described by both one- and two-compartment models [5, 6], therefore both were assessed to determine which would best describe the data. Models were evaluated by comparing the objective function values (OFV) as well as goodness-of-fit diagnostic plots and visual predictive checks. A two-compartment model calling ADVAN3 TRANS3 subroutine with first order elimination was selected (OFV 600.03). The estimated values of parameters (with relative standard error) were as follows:

Clearance = 0.38 L/day (12.4 %)
Steady-state volume of distribution = 4.26 L (23.2 %)
Intercompartmental clearance = 0.16 L/day (the value was fixed)
Central volume of distribution= 1.05 L (the value was fixed)
Inter-individual variability on clearance = 0.37 (28 %)
Proportional error = 0.66 (8.6%)
Additive error = 0.93 (37.8%)
Compared to data available in the literature, the obtained value of IFX CL in our patient population was slightly higher, probably due to disease severity and inflammation status of patients. Therefore, further analysis of covariate effects and exposure-response relationship will be explored in further research.

Conclusion: These preliminary results suggest that patients with fistulising form of Crohn’s disease may have higher IFX clearance and since higher trough concentrations are associated with fistulae healing, dose increase and/or dosing interval shortening could be beneficial to achieve disease remission.



References:

[1]    Gecse K, Khanna R, Stoker J, Jenkins JT, Gabe S, Hahnloser D, D’Haens G. Fistulizing Crohn’s disease: Diagnosis and management. United European gastroenterology journal. 2013 Jun;1(3):206-13.
[2]    Gu B, Venkatesh K, Williams AJ, Ng W, Corte C, Gholamrezaei A, Ghaly S, Xuan W, Paramsothy S, Connor S. Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn’s disease. World journal of gastroenterology. 2022 Jun 6;28(23):2597.
[3]    Owen JS, Fiedler-Kelly J. Introduction to population pharmacokinetic/pharmacodynamic analysis with nonlinear mixed effects models. John Wiley & Sons; 2014 Jun 19.
[4]    Beal SL. Ways to fit a PK model with some data below the quantification limit. Journal of pharmacokinetics and pharmacodynamics. 2001 Oct 1;28(5):481.
[5]    Konecki C, Feliu C, Cazaubon Y, Giusti D, Tonye-Libyh M, Brixi H, Cadiot G, Biron A, Djerada Z. External evaluation of population pharmacokinetic models and Bayes-based dosing of infliximab. Pharmaceutics. 2021 Aug 3;13(8):1191.
[6]    Schräpel C, Kovar L, Selzer D, Hofmann U, Tran F, Reinisch W, Schwab M, Lehr T. External model performance evaluation of twelve infliximab population pharmacokinetic models in patients with inflammatory bowel disease. Pharmaceutics. 2021 Aug 31;13(9):1368.
C3  - Page. Abstracts of the Annual Meeting of the Population Approach Group in Europe
T1  - Population pharmacokinetic model of infliximab in patients with fistulising Crohn’s disease
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4898
ER  - 

@conference{
author = "Homšek, Ana and Marković, Srđan and Kralj, Đorđe and Odanović, Olga and Svorcan, Petar and Jovanović, Marija and Vučićević, Katarina",
year = "2023",
abstract = "Introduction: Infliximab (IFX), anti-tumour necrosis factor alpha antibody, is widely used in the treatment of inflammatory bowel diseases. Patients with Crohn’s disease may develop a more complicated form which involves fistulae formation, most commonly perianal. IFX has been effective in inducing fistula closure and maintaining disease remission [1]. In order to achieve fistulae healing adequate trough concentrations should be achieved [2].

Objectives:

Obtaining PK parameters for patients with the fistulising disease form
Comparing the results to the ones available in the literature for Crohn’s disease
Methods: In a retrospective review of medical documentation (from 2013 to present), 42 patients (64% male, 18-65 years old) with fistulising Crohn’s disease were selected for analysis. IFX concentrations were measured just before dose administration (trough concentration) or earlier if the patient was experiencing severe disease symptoms. For the majority of patients concentration was measured at week 14, right before the first maintenance dose. Additional concentrations were obtained at scheduled check-ups or after patients experienced signs of relapse. After appropriate premedication, each patient received the calculated fixed dose based on their body weight (dose range was 200-800 mg) via two-hour infusion. The drug was administered according to the standard (week 0, 2 and 6) and accelerated induction (every two weeks) protocols, followed by maintenance therapy (every 4, 6 or 8 weeks). Population modelling approach was applied to characterize pharmacokinetic profile of IFX using NONMEM 7.3 software (ICON Development Solutions Inc., Dublin, Ireland) [3]. The obtained data were processed using Microsoft Excel and R software.

Results: After exclusion of concentrations over the upper limit of quantification (12 μg/mL), a total of 161 concentrations were analysed. IFX concentrations below lower limit of quantification were accounted for using the M5 method [4]. Pharmacokinetics of IFX has, so far, been described by both one- and two-compartment models [5, 6], therefore both were assessed to determine which would best describe the data. Models were evaluated by comparing the objective function values (OFV) as well as goodness-of-fit diagnostic plots and visual predictive checks. A two-compartment model calling ADVAN3 TRANS3 subroutine with first order elimination was selected (OFV 600.03). The estimated values of parameters (with relative standard error) were as follows:

Clearance = 0.38 L/day (12.4 %)
Steady-state volume of distribution = 4.26 L (23.2 %)
Intercompartmental clearance = 0.16 L/day (the value was fixed)
Central volume of distribution= 1.05 L (the value was fixed)
Inter-individual variability on clearance = 0.37 (28 %)
Proportional error = 0.66 (8.6%)
Additive error = 0.93 (37.8%)
Compared to data available in the literature, the obtained value of IFX CL in our patient population was slightly higher, probably due to disease severity and inflammation status of patients. Therefore, further analysis of covariate effects and exposure-response relationship will be explored in further research.

Conclusion: These preliminary results suggest that patients with fistulising form of Crohn’s disease may have higher IFX clearance and since higher trough concentrations are associated with fistulae healing, dose increase and/or dosing interval shortening could be beneficial to achieve disease remission.



References:

[1]    Gecse K, Khanna R, Stoker J, Jenkins JT, Gabe S, Hahnloser D, D’Haens G. Fistulizing Crohn’s disease: Diagnosis and management. United European gastroenterology journal. 2013 Jun;1(3):206-13.
[2]    Gu B, Venkatesh K, Williams AJ, Ng W, Corte C, Gholamrezaei A, Ghaly S, Xuan W, Paramsothy S, Connor S. Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn’s disease. World journal of gastroenterology. 2022 Jun 6;28(23):2597.
[3]    Owen JS, Fiedler-Kelly J. Introduction to population pharmacokinetic/pharmacodynamic analysis with nonlinear mixed effects models. John Wiley & Sons; 2014 Jun 19.
[4]    Beal SL. Ways to fit a PK model with some data below the quantification limit. Journal of pharmacokinetics and pharmacodynamics. 2001 Oct 1;28(5):481.
[5]    Konecki C, Feliu C, Cazaubon Y, Giusti D, Tonye-Libyh M, Brixi H, Cadiot G, Biron A, Djerada Z. External evaluation of population pharmacokinetic models and Bayes-based dosing of infliximab. Pharmaceutics. 2021 Aug 3;13(8):1191.
[6]    Schräpel C, Kovar L, Selzer D, Hofmann U, Tran F, Reinisch W, Schwab M, Lehr T. External model performance evaluation of twelve infliximab population pharmacokinetic models in patients with inflammatory bowel disease. Pharmaceutics. 2021 Aug 31;13(9):1368.",
journal = "Page. Abstracts of the Annual Meeting of the Population Approach Group in Europe",
title = "Population pharmacokinetic model of infliximab in patients with fistulising Crohn’s disease",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4898"
}

Homšek, A., Marković, S., Kralj, Đ., Odanović, O., Svorcan, P., Jovanović, M.,& Vučićević, K.. (2023). Population pharmacokinetic model of infliximab in patients with fistulising Crohn’s disease. in Page. Abstracts of the Annual Meeting of the Population Approach Group in Europe.
https://hdl.handle.net/21.15107/rcub_farfar_4898

Homšek A, Marković S, Kralj Đ, Odanović O, Svorcan P, Jovanović M, Vučićević K. Population pharmacokinetic model of infliximab in patients with fistulising Crohn’s disease. in Page. Abstracts of the Annual Meeting of the Population Approach Group in Europe. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_4898 .

Homšek, Ana, Marković, Srđan, Kralj, Đorđe, Odanović, Olga, Svorcan, Petar, Jovanović, Marija, Vučićević, Katarina, "Population pharmacokinetic model of infliximab in patients with fistulising Crohn’s disease" in Page. Abstracts of the Annual Meeting of the Population Approach Group in Europe (2023),
https://hdl.handle.net/21.15107/rcub_farfar_4898 .

TY  - CONF
AU  - Marković, Srđan
AU  - Kralj, Đorđe
AU  - Odanović, Olga
AU  - Homšek, Ana
AU  - Kalaba, Ana
AU  - Svorcan, Petar
AU  - Vučićević, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4828
PB  - Oxford Academic Press
C3  - Journal of Crohn's and Colitis
T1  - Pharmacokinetics and clinical evaluation of vedolizumab based on real-life routine monitoring data in IBD patients
VL  - 17
IS  - Supplement 1
SP  - i925
EP  - i925
DO  - 10.1093/ecco-jcc/jjac190.0922
ER  - 

@conference{
author = "Marković, Srđan and Kralj, Đorđe and Odanović, Olga and Homšek, Ana and Kalaba, Ana and Svorcan, Petar and Vučićević, Katarina",
year = "2023",
publisher = "Oxford Academic Press",
journal = "Journal of Crohn's and Colitis",
title = "Pharmacokinetics and clinical evaluation of vedolizumab based on real-life routine monitoring data in IBD patients",
volume = "17",
number = "Supplement 1",
pages = "i925-i925",
doi = "10.1093/ecco-jcc/jjac190.0922"
}

Marković, S., Kralj, Đ., Odanović, O., Homšek, A., Kalaba, A., Svorcan, P.,& Vučićević, K.. (2023). Pharmacokinetics and clinical evaluation of vedolizumab based on real-life routine monitoring data in IBD patients. in Journal of Crohn's and Colitis
Oxford Academic Press., 17(Supplement 1), i925-i925.
https://doi.org/10.1093/ecco-jcc/jjac190.0922

Marković S, Kralj Đ, Odanović O, Homšek A, Kalaba A, Svorcan P, Vučićević K. Pharmacokinetics and clinical evaluation of vedolizumab based on real-life routine monitoring data in IBD patients. in Journal of Crohn's and Colitis. 2023;17(Supplement 1):i925-i925.
doi:10.1093/ecco-jcc/jjac190.0922 .

Marković, Srđan, Kralj, Đorđe, Odanović, Olga, Homšek, Ana, Kalaba, Ana, Svorcan, Petar, Vučićević, Katarina, "Pharmacokinetics and clinical evaluation of vedolizumab based on real-life routine monitoring data in IBD patients" in Journal of Crohn's and Colitis, 17, no. Supplement 1 (2023):i925-i925,
https://doi.org/10.1093/ecco-jcc/jjac190.0922 . .

TY  - CONF
AU  - Vezmar-Kovačević, Sandra
AU  - Odalović, Marina
AU  - Tadić, Ivana
AU  - Vučićević, Katarina
AU  - Malenović, Anđelija
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4822
AB  - Introduction: At the Faculty of Pharmacy University of Belgrade, the Objective Structured Clinical Examination (0SCE) was introduced to assess clinical competences and communication skills of pharmacy students following their 6-weeks practice in public pharmacies during the 10th semester. Methods: The OSCE consisted of one patient case that was presented to the student firstly in a short written form. The patient case had at least one drug-related problem that the student was expected to identify and solve. A teaching assistant played the role of the patient and a teacher assessed the communication skills and clinical competences during the student's interview with the „patient" using a structured form (checklist). The student had limited time (7 minutes) to identify and solve the drug-related problem(s) and to councel the patient. The use of a Drug register and Pharmacotherapy guide were allowed. Results: One hundred fifty students completed the OSCE so far. The students could achieve O-40 points during the exam, according to their performance. The maximal point score was achieved if the student obtained all relevant information from the patient”, identified and solved the drug-related problem(s) and offered appropriate information. The minimal point score (0) was assigned if the student made an error which could harm the patient. The median result of the OSCE was 28 points (interquatile range 10), while 7 students (4.7%) scored 0-9 points, 12 (8.0%) scored 10-19 points, 68 (45.3%) scored 20-29 points, 58 (38.79%) scored 30-39 points and 5 students (3.3%) scored 40 points. Conclusions: The introduction of the OSCE was successful and enabled the teaching staff to obtain a more accurate knowledge of the students’ clinical competences and communication skills as well as to identify gaps in the competences in skills which need to be improved.
PB  - European Association of Faculties of Pharmacy
C3  - EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book
T1  - Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia
SP  - 47
EP  - 47
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4822
ER  - 

@conference{
author = "Vezmar-Kovačević, Sandra and Odalović, Marina and Tadić, Ivana and Vučićević, Katarina and Malenović, Anđelija",
year = "2022",
abstract = "Introduction: At the Faculty of Pharmacy University of Belgrade, the Objective Structured Clinical Examination (0SCE) was introduced to assess clinical competences and communication skills of pharmacy students following their 6-weeks practice in public pharmacies during the 10th semester. Methods: The OSCE consisted of one patient case that was presented to the student firstly in a short written form. The patient case had at least one drug-related problem that the student was expected to identify and solve. A teaching assistant played the role of the patient and a teacher assessed the communication skills and clinical competences during the student's interview with the „patient" using a structured form (checklist). The student had limited time (7 minutes) to identify and solve the drug-related problem(s) and to councel the patient. The use of a Drug register and Pharmacotherapy guide were allowed. Results: One hundred fifty students completed the OSCE so far. The students could achieve O-40 points during the exam, according to their performance. The maximal point score was achieved if the student obtained all relevant information from the patient”, identified and solved the drug-related problem(s) and offered appropriate information. The minimal point score (0) was assigned if the student made an error which could harm the patient. The median result of the OSCE was 28 points (interquatile range 10), while 7 students (4.7%) scored 0-9 points, 12 (8.0%) scored 10-19 points, 68 (45.3%) scored 20-29 points, 58 (38.79%) scored 30-39 points and 5 students (3.3%) scored 40 points. Conclusions: The introduction of the OSCE was successful and enabled the teaching staff to obtain a more accurate knowledge of the students’ clinical competences and communication skills as well as to identify gaps in the competences in skills which need to be improved.",
publisher = "European Association of Faculties of Pharmacy",
journal = "EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book",
title = "Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia",
pages = "47-47",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4822"
}

Vezmar-Kovačević, S., Odalović, M., Tadić, I., Vučićević, K.,& Malenović, A.. (2022). Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia. in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book
European Association of Faculties of Pharmacy., 47-47.
https://hdl.handle.net/21.15107/rcub_farfar_4822

Vezmar-Kovačević S, Odalović M, Tadić I, Vučićević K, Malenović A. Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia. in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book. 2022;:47-47.
https://hdl.handle.net/21.15107/rcub_farfar_4822 .

Vezmar-Kovačević, Sandra, Odalović, Marina, Tadić, Ivana, Vučićević, Katarina, Malenović, Anđelija, "Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia" in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book (2022):47-47,
https://hdl.handle.net/21.15107/rcub_farfar_4822 .

TY  - JOUR
AU  - Garcia-Cremades, Maria
AU  - Vučićević, Katarina
AU  - Hendrix, Craig W
AU  - Jayachandran, Priya
AU  - Jarlsberg, Leah
AU  - Grant, Robert
AU  - Celum, Connie L.
AU  - Martin, Michael
AU  - Baeten, Jared M.
AU  - Marrazzo, Jeanne
AU  - Anderson, Peter
AU  - Choopanya, Kachit
AU  - Vanichseni, Suphak
AU  - Glidden, David V.
AU  - Savić, Radojka M.
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4338
AB  - Background. Daily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration. Methods. Participant data from TFV-based daily oral and topical active arms of phase 3 trials (iPrEx, VOICE, and Partners PrEP) were pooled (n = 2950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models. Results. Around 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (≏90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high-risk females (45.8 ng/mL) compared with high-risk males (16.1 ng/mL) and to low-risk individuals (≏7.5 ng/mL). Dosing simulations indicated that high-risk women require full adherence to maintain protective levels. Conclusions. Using the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high-risk females need higher levels of plasma TFV to achieve HIV protection compared with males. HIV protection exceeds 90% in all populations if daily adherence is achieved.
PB  - Oxford University Press
T2  - Clinical Infectious Diseases
T1  - Characterizing HIV-Preventive, Plasma Tenofovir Concentrations-A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis (PrEP) Clinical Trials
VL  - 75
IS  - 11
SP  - 1873
EP  - 1882
DO  - 10.1093/cid/ciac313
ER  - 

@article{
author = "Garcia-Cremades, Maria and Vučićević, Katarina and Hendrix, Craig W and Jayachandran, Priya and Jarlsberg, Leah and Grant, Robert and Celum, Connie L. and Martin, Michael and Baeten, Jared M. and Marrazzo, Jeanne and Anderson, Peter and Choopanya, Kachit and Vanichseni, Suphak and Glidden, David V. and Savić, Radojka M.",
year = "2022",
abstract = "Background. Daily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration. Methods. Participant data from TFV-based daily oral and topical active arms of phase 3 trials (iPrEx, VOICE, and Partners PrEP) were pooled (n = 2950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models. Results. Around 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (≏90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high-risk females (45.8 ng/mL) compared with high-risk males (16.1 ng/mL) and to low-risk individuals (≏7.5 ng/mL). Dosing simulations indicated that high-risk women require full adherence to maintain protective levels. Conclusions. Using the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high-risk females need higher levels of plasma TFV to achieve HIV protection compared with males. HIV protection exceeds 90% in all populations if daily adherence is achieved.",
publisher = "Oxford University Press",
journal = "Clinical Infectious Diseases",
title = "Characterizing HIV-Preventive, Plasma Tenofovir Concentrations-A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis (PrEP) Clinical Trials",
volume = "75",
number = "11",
pages = "1873-1882",
doi = "10.1093/cid/ciac313"
}

Garcia-Cremades, M., Vučićević, K., Hendrix, C. W., Jayachandran, P., Jarlsberg, L., Grant, R., Celum, C. L., Martin, M., Baeten, J. M., Marrazzo, J., Anderson, P., Choopanya, K., Vanichseni, S., Glidden, D. V.,& Savić, R. M.. (2022). Characterizing HIV-Preventive, Plasma Tenofovir Concentrations-A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis (PrEP) Clinical Trials. in Clinical Infectious Diseases
Oxford University Press., 75(11), 1873-1882.
https://doi.org/10.1093/cid/ciac313

Garcia-Cremades M, Vučićević K, Hendrix CW, Jayachandran P, Jarlsberg L, Grant R, Celum CL, Martin M, Baeten JM, Marrazzo J, Anderson P, Choopanya K, Vanichseni S, Glidden DV, Savić RM. Characterizing HIV-Preventive, Plasma Tenofovir Concentrations-A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis (PrEP) Clinical Trials. in Clinical Infectious Diseases. 2022;75(11):1873-1882.
doi:10.1093/cid/ciac313 .

Garcia-Cremades, Maria, Vučićević, Katarina, Hendrix, Craig W, Jayachandran, Priya, Jarlsberg, Leah, Grant, Robert, Celum, Connie L., Martin, Michael, Baeten, Jared M., Marrazzo, Jeanne, Anderson, Peter, Choopanya, Kachit, Vanichseni, Suphak, Glidden, David V., Savić, Radojka M., "Characterizing HIV-Preventive, Plasma Tenofovir Concentrations-A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis (PrEP) Clinical Trials" in Clinical Infectious Diseases, 75, no. 11 (2022):1873-1882,
https://doi.org/10.1093/cid/ciac313 . .

TY  - CONF
AU  - Roganović, Maša
AU  - Cvetković, Mirjana
AU  - Gojković, Ivana
AU  - Spasojević, Brankica
AU  - Kostić, Mirjana
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4532
AB  - Cyclosporin A (CyA) is an immunosuppressant used as part of a post-transplant
therapeutic protocol to prevent graft rejection. Due to the large pharmacokinetic variability
that characterizes it, it is necessary to conduct therapeutic drug monitoring (TDM). The aim
of the conducted research is to assess the exposure of CyA in the period of up to 3 months
after transplantation (early post-transplantation period) with the identification of factors
that influence the values of the pharmacokinetic parameters of CyA. From pediatric patients
with kidney transplants, at the University Children ́s Hospital Tiršova, data about dosage
regimens, cotherapy, and measured CyA concentrations (C0 - immediately before the next
dose and C2 - 2 hours after the morning dose) were collected retrospectively. Data were
analysed in NONMEM® (version 7.4). Twenty six patients (up to 12 years old) were
included in the analysis. The pharmacokinetic model that best described the data is a one-
compartment model with first-order absorption. Haematocrit, serum creatinine and body
mass were identified as the main factors of variability. In further analysis, it is necessary to
include data about genetic polymorphism, which is expected to have the greatest impact on
drug exposure and change the power ratio of factors that influence CyA parameter values
and concentrations.The obtained results are expected considering the characteristics of CyA.
In addition to identification, quantification of the influence of the mentioned factors is crucial
for establishing an optimal dosing regimen in the early post-transplantation period in
children, when the risk of graft rejection is the highest.
AB  - Ciklosporin A (CyA) je imunosupresiv koji se koristi kao deo posttransplantacionog
terapijskog protokola u cilju prevencije odbacivanja grafta. Zbog velike farmakokinetičke
varijabilnosti koja ga karakteriše, neophodno je sprovođenje terapijskog monitoringa
(therapeutic drug monitoring, TDM). Cilj sprovedenog istraživanja je procena izloženosti CyA
u periodu do 3 meseca nakon transplantacije (rani posttransplantacioni period) uz
identifikaciju faktora koji utiču na vrednosti farmakokinetičkih parametara CyA. Od
pedijatrijskih pacijenata sa transplantiranim bubregom, u Univerzitetskoj klinici Tiršova,
retrospektivno su prikupljani podaci o primenjenoj dozi CyA, koterapiji, izmerenim
koncentracijama CyA (C0 – neposredno pred davanje naredne doze i C2 – 2 sata nakon
jutarnje doze) i vrednostima laboratorijskih parametara od značaja. Podaci su obrađivani
upotrebom populacione farmakokinetičke analize u programu NONMEM® (verzija 7.4). U
analizu je uključeno 26 pacijenata starosti do 12 godina. Farmakokinetički model koji
najbolje opisuje dostupne podatke je jednoprostorni model sa apsorpcijom prvog reda. Kao
glavni faktori varijabilnosti identifikovani su hematokrit, serumski kreatinin i telesna masa.
U daljoj analizi, neophodno je uključiti podatke o genetskom polimorfizmu, za koje se
očekuje da će imati najveći uticaj na izloženost leku i promeniti odnos snaga faktora koji
utiču na vrednosti parametara CyA i koncentraciju. Dobijeni rezultati su očekivani imajući u
vidu karakteristike CyA. Pored identifikacije, i kvantifikacija uticaja navedenih faktora je
ključna za uspostavljanje optimalnog režima doziranja u ranom posttransplantacionom
periodu kod dece, kada je rizik od odbacivanja grafta najveći.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period
T1  - Procena izloženosti ciklosporinu a i identifikacija faktora varijabilnosti u ranom posttransplantacionom periodu
VL  - 72
IS  - 4 suplement
SP  - S304
EP  - S305
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4532
ER  - 

@conference{
author = "Roganović, Maša and Cvetković, Mirjana and Gojković, Ivana and Spasojević, Brankica and Kostić, Mirjana and Miljković, Branislava and Vučićević, Katarina",
year = "2022",
abstract = "Cyclosporin A (CyA) is an immunosuppressant used as part of a post-transplant
therapeutic protocol to prevent graft rejection. Due to the large pharmacokinetic variability
that characterizes it, it is necessary to conduct therapeutic drug monitoring (TDM). The aim
of the conducted research is to assess the exposure of CyA in the period of up to 3 months
after transplantation (early post-transplantation period) with the identification of factors
that influence the values of the pharmacokinetic parameters of CyA. From pediatric patients
with kidney transplants, at the University Children ́s Hospital Tiršova, data about dosage
regimens, cotherapy, and measured CyA concentrations (C0 - immediately before the next
dose and C2 - 2 hours after the morning dose) were collected retrospectively. Data were
analysed in NONMEM® (version 7.4). Twenty six patients (up to 12 years old) were
included in the analysis. The pharmacokinetic model that best described the data is a one-
compartment model with first-order absorption. Haematocrit, serum creatinine and body
mass were identified as the main factors of variability. In further analysis, it is necessary to
include data about genetic polymorphism, which is expected to have the greatest impact on
drug exposure and change the power ratio of factors that influence CyA parameter values
and concentrations.The obtained results are expected considering the characteristics of CyA.
In addition to identification, quantification of the influence of the mentioned factors is crucial
for establishing an optimal dosing regimen in the early post-transplantation period in
children, when the risk of graft rejection is the highest., Ciklosporin A (CyA) je imunosupresiv koji se koristi kao deo posttransplantacionog
terapijskog protokola u cilju prevencije odbacivanja grafta. Zbog velike farmakokinetičke
varijabilnosti koja ga karakteriše, neophodno je sprovođenje terapijskog monitoringa
(therapeutic drug monitoring, TDM). Cilj sprovedenog istraživanja je procena izloženosti CyA
u periodu do 3 meseca nakon transplantacije (rani posttransplantacioni period) uz
identifikaciju faktora koji utiču na vrednosti farmakokinetičkih parametara CyA. Od
pedijatrijskih pacijenata sa transplantiranim bubregom, u Univerzitetskoj klinici Tiršova,
retrospektivno su prikupljani podaci o primenjenoj dozi CyA, koterapiji, izmerenim
koncentracijama CyA (C0 – neposredno pred davanje naredne doze i C2 – 2 sata nakon
jutarnje doze) i vrednostima laboratorijskih parametara od značaja. Podaci su obrađivani
upotrebom populacione farmakokinetičke analize u programu NONMEM® (verzija 7.4). U
analizu je uključeno 26 pacijenata starosti do 12 godina. Farmakokinetički model koji
najbolje opisuje dostupne podatke je jednoprostorni model sa apsorpcijom prvog reda. Kao
glavni faktori varijabilnosti identifikovani su hematokrit, serumski kreatinin i telesna masa.
U daljoj analizi, neophodno je uključiti podatke o genetskom polimorfizmu, za koje se
očekuje da će imati najveći uticaj na izloženost leku i promeniti odnos snaga faktora koji
utiču na vrednosti parametara CyA i koncentraciju. Dobijeni rezultati su očekivani imajući u
vidu karakteristike CyA. Pored identifikacije, i kvantifikacija uticaja navedenih faktora je
ključna za uspostavljanje optimalnog režima doziranja u ranom posttransplantacionom
periodu kod dece, kada je rizik od odbacivanja grafta najveći.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period, Procena izloženosti ciklosporinu a i identifikacija faktora varijabilnosti u ranom posttransplantacionom periodu",
volume = "72",
number = "4 suplement",
pages = "S304-S305",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4532"
}

Roganović, M., Cvetković, M., Gojković, I., Spasojević, B., Kostić, M., Miljković, B.,& Vučićević, K.. (2022). Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S304-S305.
https://hdl.handle.net/21.15107/rcub_farfar_4532

Roganović M, Cvetković M, Gojković I, Spasojević B, Kostić M, Miljković B, Vučićević K. Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period. in Arhiv za farmaciju. 2022;72(4 suplement):S304-S305.
https://hdl.handle.net/21.15107/rcub_farfar_4532 .

Roganović, Maša, Cvetković, Mirjana, Gojković, Ivana, Spasojević, Brankica, Kostić, Mirjana, Miljković, Branislava, Vučićević, Katarina, "Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S304-S305,
https://hdl.handle.net/21.15107/rcub_farfar_4532 .

TY  - CONF
AU  - Jovanović, Marija
AU  - Ćulafić, Milica
AU  - Pejić, Nina
AU  - Štulić, Miloš
AU  - Kovačević, Milena
AU  - Vezmar-Kovačević, Sandra
AU  - Miljković, Branislava
AU  - Ćulafić, Đorđe
AU  - Vučićević, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4531
AB  - Tacrolimus is an immunosuppressant used to prevent graft rejection after liver
transplantation. The narrow therapeutic range and great variability in pharmacokinetics
indicate the need for therapy individualization. The aim of the study was to develop and
validate the base pharmacokinetic model of tacrolimus using data collected during
therapeutic drug monitoring. The study included 29 liver transplant recipients followed up
at Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. Using the
NONMEM® program, we analyzed tacrolimus concentrations (Ctrough) measured in whole
blood (260). Pharmacokinetics have been described as one-compartment model with first-
order absorption and elimination. Internal validation was performed using graphical
assessment, bootstrap method and visual predictive check (VPC). Typical value of oral
clearance (CL/F) was 30.4 L/h, while value of oral volume of distribution was 5770 L. The
value of the absorption rate constant was fixed at 4.48 h-1 . Interindividual variability was
best described by the exponential model, and residual by the additive model. Interindividual
variability for CL/F was 38.2%. Individual predicted concentrations (IPRED) showed better
agreement with the measured values than population predicted values (PRED). Conditional
weighted residuals (CWRES vs PRED, CWRES vs TIME) were mostly between -2 and +2
standard deviations. The parameters obtained by bootstrap analysis do not deviate
significantly from the model. Median, 5th and 95th percentiles in the VPC method mostly
were within the simulated 95% confidence interval. The obtained population
pharmacokinetic model, after additional optimization, can be used for individualization of
the tacrolimus dosing regimen in the population of liver transplant recipients.
AB  - Takrolimus je imunosupresiv koji se primenjuje za prevenciju odbacivanja grafta
nakon transplantacije jetre. Uzak terapijski opseg i velika varijabilnost u farmakokinetici
ukazuju na neophodnost individualizacije terapije. Cilj istraživanja bio je razvoj i validacija
osnovnog farmakokinetičkog modela takrolimusa baziranog na podacima prikupljenim
tokom terapijskog praćenja leka. Studija je uključila 29 pacijenata sa transplantiranom
jetrom, praćenih na Klinici za gastroenterologiju i hepatologiju, Kliničkog centra Srbije.
Primenom NONMEM® programa analizirane su koncentracije takrolimusa izmerene u punoj
krvi (260), neposredno pre primene jutarnje doze (Ctrough). Farmakokinetika je opisana
jednoprostornim modelom sa resorpcijom i eliminacijom prvog reda. Interna validacija je
vršena primenom grafičke metode procene, metode umnožavanja podataka (bootstrap) i
vizuelne prediktivne provere (VPC). Procenjena tipična vrednost oralnog klirensa (CL/F)
iznosila je 30,4 L/h, dok je vrednost oralnog volumena distribucije bila 5770 L. Vrednost
konstante brzine resorpcije je fiksirana na 4,48 h-1 . Interindividualna varijabilnost je najbolje
opisana eksponencijalnim modelom, a rezidualna aditivnim modelom. Zabeležena je
interindividualna varijabilnost za CL/F od 38,2%. Predviđene individualne koncentracije
(IPRED) pokazuju bolje slaganje sa izmerenim vrednostima, nego populacione predviđene
vrednosti (PRED). Uslovni težinski reziduali (CWRES vs PRED, CWRES vs TIME) su većinom
raspoređeni između -2 i +2 standardne devijacije. Parametri dobijeni bootstrap analizom ne
odstupaju značajno od modela, dok su vrednosti medijane, 5. i 95. percentila u VPC metodi
uglavnom bile u okviru simuliranih 95% intervala pouzdanosti. Dobijeni populacioni
farmakokinetički model, može se nakon dodatne optimizacije, primeniti u svrhu
individualizacije režima doziranja takrolimusa u populaciji pacijenata sa transplantiranom
jetrom.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - A population pharmacokinetic model of tacrolimus in adult liver transplant recipients
T1  - Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom
VL  - 72
IS  - 4 suplement
SP  - S298
EP  - S299
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4531
ER  - 

@conference{
author = "Jovanović, Marija and Ćulafić, Milica and Pejić, Nina and Štulić, Miloš and Kovačević, Milena and Vezmar-Kovačević, Sandra and Miljković, Branislava and Ćulafić, Đorđe and Vučićević, Katarina",
year = "2022",
abstract = "Tacrolimus is an immunosuppressant used to prevent graft rejection after liver
transplantation. The narrow therapeutic range and great variability in pharmacokinetics
indicate the need for therapy individualization. The aim of the study was to develop and
validate the base pharmacokinetic model of tacrolimus using data collected during
therapeutic drug monitoring. The study included 29 liver transplant recipients followed up
at Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. Using the
NONMEM® program, we analyzed tacrolimus concentrations (Ctrough) measured in whole
blood (260). Pharmacokinetics have been described as one-compartment model with first-
order absorption and elimination. Internal validation was performed using graphical
assessment, bootstrap method and visual predictive check (VPC). Typical value of oral
clearance (CL/F) was 30.4 L/h, while value of oral volume of distribution was 5770 L. The
value of the absorption rate constant was fixed at 4.48 h-1 . Interindividual variability was
best described by the exponential model, and residual by the additive model. Interindividual
variability for CL/F was 38.2%. Individual predicted concentrations (IPRED) showed better
agreement with the measured values than population predicted values (PRED). Conditional
weighted residuals (CWRES vs PRED, CWRES vs TIME) were mostly between -2 and +2
standard deviations. The parameters obtained by bootstrap analysis do not deviate
significantly from the model. Median, 5th and 95th percentiles in the VPC method mostly
were within the simulated 95% confidence interval. The obtained population
pharmacokinetic model, after additional optimization, can be used for individualization of
the tacrolimus dosing regimen in the population of liver transplant recipients., Takrolimus je imunosupresiv koji se primenjuje za prevenciju odbacivanja grafta
nakon transplantacije jetre. Uzak terapijski opseg i velika varijabilnost u farmakokinetici
ukazuju na neophodnost individualizacije terapije. Cilj istraživanja bio je razvoj i validacija
osnovnog farmakokinetičkog modela takrolimusa baziranog na podacima prikupljenim
tokom terapijskog praćenja leka. Studija je uključila 29 pacijenata sa transplantiranom
jetrom, praćenih na Klinici za gastroenterologiju i hepatologiju, Kliničkog centra Srbije.
Primenom NONMEM® programa analizirane su koncentracije takrolimusa izmerene u punoj
krvi (260), neposredno pre primene jutarnje doze (Ctrough). Farmakokinetika je opisana
jednoprostornim modelom sa resorpcijom i eliminacijom prvog reda. Interna validacija je
vršena primenom grafičke metode procene, metode umnožavanja podataka (bootstrap) i
vizuelne prediktivne provere (VPC). Procenjena tipična vrednost oralnog klirensa (CL/F)
iznosila je 30,4 L/h, dok je vrednost oralnog volumena distribucije bila 5770 L. Vrednost
konstante brzine resorpcije je fiksirana na 4,48 h-1 . Interindividualna varijabilnost je najbolje
opisana eksponencijalnim modelom, a rezidualna aditivnim modelom. Zabeležena je
interindividualna varijabilnost za CL/F od 38,2%. Predviđene individualne koncentracije
(IPRED) pokazuju bolje slaganje sa izmerenim vrednostima, nego populacione predviđene
vrednosti (PRED). Uslovni težinski reziduali (CWRES vs PRED, CWRES vs TIME) su većinom
raspoređeni između -2 i +2 standardne devijacije. Parametri dobijeni bootstrap analizom ne
odstupaju značajno od modela, dok su vrednosti medijane, 5. i 95. percentila u VPC metodi
uglavnom bile u okviru simuliranih 95% intervala pouzdanosti. Dobijeni populacioni
farmakokinetički model, može se nakon dodatne optimizacije, primeniti u svrhu
individualizacije režima doziranja takrolimusa u populaciji pacijenata sa transplantiranom
jetrom.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "A population pharmacokinetic model of tacrolimus in adult liver transplant recipients, Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom",
volume = "72",
number = "4 suplement",
pages = "S298-S299",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4531"
}

Jovanović, M., Ćulafić, M., Pejić, N., Štulić, M., Kovačević, M., Vezmar-Kovačević, S., Miljković, B., Ćulafić, Đ.,& Vučićević, K.. (2022). A population pharmacokinetic model of tacrolimus in adult liver transplant recipients. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S298-S299.
https://hdl.handle.net/21.15107/rcub_farfar_4531

Jovanović M, Ćulafić M, Pejić N, Štulić M, Kovačević M, Vezmar-Kovačević S, Miljković B, Ćulafić Đ, Vučićević K. A population pharmacokinetic model of tacrolimus in adult liver transplant recipients. in Arhiv za farmaciju. 2022;72(4 suplement):S298-S299.
https://hdl.handle.net/21.15107/rcub_farfar_4531 .

Jovanović, Marija, Ćulafić, Milica, Pejić, Nina, Štulić, Miloš, Kovačević, Milena, Vezmar-Kovačević, Sandra, Miljković, Branislava, Ćulafić, Đorđe, Vučićević, Katarina, "A population pharmacokinetic model of tacrolimus in adult liver transplant recipients" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S298-S299,
https://hdl.handle.net/21.15107/rcub_farfar_4531 .

TY  - CONF
AU  - Škorić, Biljana
AU  - Jovanović, Marija
AU  - Miljković, Branislava
AU  - Kuzmanović, Miloš
AU  - Vučićević, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4529
AB  - Administration of high dose methotrexate (HDMTX) is common part of pediatric
protocols for acute lymphoblastic leukemia (ALL) and non-Hodking lymphoma (NHL).
Methotrexate is used in certain phase of therapy in doses 3 g/m 2 or 5 g/m 2 with the objective
to achieve concentration that will ensure eradication of tumor cells with minimal toxic effect.
The aim of this study is overview of drug concentration and assessment of therapy safety in
relation to referent values. After obtaining Ethics committee approval at The Institute for
mother and child Healthcare of Serbia “Dr Vukan Cupic” 50 pediatric patients with ALL or
NHL were enrolled. Data on MTX usage was retrospectively collected from the patient
history. Concentrations and normalized concentrations per applied dose were compared
with nonparametric tests in SPSS (version 18). MTX concentration mean (± standard
deviation) following administration of 3 g/m 2 respectively 5 g/m2 doses were 19.72±6.62
mg/L respectively 34.73±17.13 at 24 h, 0.20±0.36 mg/L respectively 0.24±0.58 mg/L at 48h
and 0.14±0.44 mg/L respectively 0.12±0.89 mg/L at 72h after start of the infusion.
Statistically significant difference (p<0.001) is only seen at 24h concentration between 3
g/m 2 (mean rank 43.97) and 5 g/m 2 (mean rank 103.36). In all other time points, there was
no difference during comparison of concentrations nor normalized concentration, even
though it is seen trend of higher values in 5 g/m2 group. Results of analysis show that
administration of higher dose during simultaneous distribution and elimination phase leads
to higher concentrations while during elimination phase this effect is less visible. However,
administration of the high doses brings the risk of side effects due to reaching higher
concentrations.
AB  - Primena visokih doza metotreksata je uobičajena u pedijatrijskim protokolima za
lečenje akutne limfoblastne leukemije (ALL) i non-Hodking limfoma (NHL). Metotreksat se u
određenoj fazi terapije primenje u dozi od 3 g/m2 ili 5 g/m 2 u cilju postizanja koncentracije
koje uništavaju tumorske ćelije uz minimalan toksičan efekat. Cilj ovog rada je prikaz
koncentracije leka u zavisnosti od primenjene doze i procena bezbednosti terapije u odnosu
na referentne vrednosti koncentracije. Nakon odobrenja etičkog odbora Instituta za
zdravstvenu zaštitu majke i deteta Srbije „Dr Vukan Čupić“ uključeno je 50 pedijatrijski
pacijenata sa ALL ili NHL. Podaci o primeni MTX su retrospektivno prikupljeni iz istorija
bolesti. Koncentracije i normalizovane koncentracije po primenjenoj dozi su statistički
analizirani neparametarskim testovima u SPSS-u (verzija 18). Srednja vrednost
koncentracija (± standardna devijacija) MTX pri primeni 3 g/m2 odnosno 5 g/m2 je iznosila
19,72±6,62 mg/L odnosno 34,73±17,13 u 24h, 0,20±0,36 mg/L odnosno 0,24±0,58 mg/L u
48h i 0,14±0,44 mg/L odnosno 0,12±0,89 mg/L u 72h posle početka infuzije. Statistički
značajna razlika (p<0,001) je uočena kod koncentracija u 24h između doza 3 g/m2 (mean
rank = 43,97) i 5 g/m2 (mean rank= 103,36). U ostalim vremenskim tačkama i pri poređenju
normalizovanih koncentracija nije bilo statistički značajne razlike, iako je primetan trend
viših vrednosti u grupi 5 g/m 2 . Rezultati analize pokazuju da pri primeni veće doze leka
tokom istovremene distribucije i eliminacije leka postoji mogućnost detektovanja visokih
koncentracija, dok je tokom faze eliminacije uticaj primenjene doze manje uočljiv. Ipak,
primena veće doze nosi rizik od neželjenih efekata.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles
T1  - Ispitivanje koncentracija i normalizovanih koncentracija metotreksata u zavisnosti od primenjene doze u pedijatrijskoj populaciji sa ALL i NHL
VL  - 72
IS  - 4 suplement
SP  - S290
EP  - S291
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4529
ER  - 

@conference{
author = "Škorić, Biljana and Jovanović, Marija and Miljković, Branislava and Kuzmanović, Miloš and Vučićević, Katarina",
year = "2022",
abstract = "Administration of high dose methotrexate (HDMTX) is common part of pediatric
protocols for acute lymphoblastic leukemia (ALL) and non-Hodking lymphoma (NHL).
Methotrexate is used in certain phase of therapy in doses 3 g/m 2 or 5 g/m 2 with the objective
to achieve concentration that will ensure eradication of tumor cells with minimal toxic effect.
The aim of this study is overview of drug concentration and assessment of therapy safety in
relation to referent values. After obtaining Ethics committee approval at The Institute for
mother and child Healthcare of Serbia “Dr Vukan Cupic” 50 pediatric patients with ALL or
NHL were enrolled. Data on MTX usage was retrospectively collected from the patient
history. Concentrations and normalized concentrations per applied dose were compared
with nonparametric tests in SPSS (version 18). MTX concentration mean (± standard
deviation) following administration of 3 g/m 2 respectively 5 g/m2 doses were 19.72±6.62
mg/L respectively 34.73±17.13 at 24 h, 0.20±0.36 mg/L respectively 0.24±0.58 mg/L at 48h
and 0.14±0.44 mg/L respectively 0.12±0.89 mg/L at 72h after start of the infusion.
Statistically significant difference (p<0.001) is only seen at 24h concentration between 3
g/m 2 (mean rank 43.97) and 5 g/m 2 (mean rank 103.36). In all other time points, there was
no difference during comparison of concentrations nor normalized concentration, even
though it is seen trend of higher values in 5 g/m2 group. Results of analysis show that
administration of higher dose during simultaneous distribution and elimination phase leads
to higher concentrations while during elimination phase this effect is less visible. However,
administration of the high doses brings the risk of side effects due to reaching higher
concentrations., Primena visokih doza metotreksata je uobičajena u pedijatrijskim protokolima za
lečenje akutne limfoblastne leukemije (ALL) i non-Hodking limfoma (NHL). Metotreksat se u
određenoj fazi terapije primenje u dozi od 3 g/m2 ili 5 g/m 2 u cilju postizanja koncentracije
koje uništavaju tumorske ćelije uz minimalan toksičan efekat. Cilj ovog rada je prikaz
koncentracije leka u zavisnosti od primenjene doze i procena bezbednosti terapije u odnosu
na referentne vrednosti koncentracije. Nakon odobrenja etičkog odbora Instituta za
zdravstvenu zaštitu majke i deteta Srbije „Dr Vukan Čupić“ uključeno je 50 pedijatrijski
pacijenata sa ALL ili NHL. Podaci o primeni MTX su retrospektivno prikupljeni iz istorija
bolesti. Koncentracije i normalizovane koncentracije po primenjenoj dozi su statistički
analizirani neparametarskim testovima u SPSS-u (verzija 18). Srednja vrednost
koncentracija (± standardna devijacija) MTX pri primeni 3 g/m2 odnosno 5 g/m2 je iznosila
19,72±6,62 mg/L odnosno 34,73±17,13 u 24h, 0,20±0,36 mg/L odnosno 0,24±0,58 mg/L u
48h i 0,14±0,44 mg/L odnosno 0,12±0,89 mg/L u 72h posle početka infuzije. Statistički
značajna razlika (p<0,001) je uočena kod koncentracija u 24h između doza 3 g/m2 (mean
rank = 43,97) i 5 g/m2 (mean rank= 103,36). U ostalim vremenskim tačkama i pri poređenju
normalizovanih koncentracija nije bilo statistički značajne razlike, iako je primetan trend
viših vrednosti u grupi 5 g/m 2 . Rezultati analize pokazuju da pri primeni veće doze leka
tokom istovremene distribucije i eliminacije leka postoji mogućnost detektovanja visokih
koncentracija, dok je tokom faze eliminacije uticaj primenjene doze manje uočljiv. Ipak,
primena veće doze nosi rizik od neželjenih efekata.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles, Ispitivanje koncentracija i normalizovanih koncentracija metotreksata u zavisnosti od primenjene doze u pedijatrijskoj populaciji sa ALL i NHL",
volume = "72",
number = "4 suplement",
pages = "S290-S291",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4529"
}

Škorić, B., Jovanović, M., Miljković, B., Kuzmanović, M.,& Vučićević, K.. (2022). Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S290-S291.
https://hdl.handle.net/21.15107/rcub_farfar_4529

Škorić B, Jovanović M, Miljković B, Kuzmanović M, Vučićević K. Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles. in Arhiv za farmaciju. 2022;72(4 suplement):S290-S291.
https://hdl.handle.net/21.15107/rcub_farfar_4529 .

Škorić, Biljana, Jovanović, Marija, Miljković, Branislava, Kuzmanović, Miloš, Vučićević, Katarina, "Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S290-S291,
https://hdl.handle.net/21.15107/rcub_farfar_4529 .

TY  - CONF
AU  - Pejčić, Zorica
AU  - Vučićević, Katarina
AU  - García Arieta, Alfredo
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4526
AB  - Generic medicines are bioequivalent (BE) and switchable with the reference medicine,
however, between generics BE is not demonstrated. In practice, patients are often offered
generic substitution, where information on BE between generics may be useful, especially
when there is a doubt that substitution may potentially pose a risk to the patient. These
information can be obtained by assessing BE between generics, applying the method of
adjusted indirect comparison (AIC). This method is based on data from BE studies in which
generics were compared with the same reference medicine. Thus, it is possible to identify
generics for which efficacy and safety problems are not expected upon substitution (1,2).
The AIC was used to compare four generic clopidogrel medicines. Publicly available data
from original BE studies, in which each generic medicine was compared with the reference
medicine Plavix film-coated tablets 75 mg, were analysed. Generics were considered BE if the
90% confidence interval (CI) for the ratio of their pharmacokinetic parameters maximum
plasma concentration (Cmax) and area under the curve up to the last measurable
concentration (PIK 0-t), was within the acceptance range 80.00-125.00%. In all the tested
combinations, 90% CIs for PIK0-t were within the acceptance range, while for C max 90% CIs
were within or very close to the limits, with the point estimate being within the range in all
cases. The results obtained by the AIC indicated that the bioavailability of these four generic
clopidogrel medicines is very similar, therefore they can be considered switchable with each
other in clinical practice.
AB  - Generički lekovi su biološki ekvivalentni (BE) i zamenjivi sa referentnim lekom,
međutim, između samih generičkih lekova BE nije potvrđena. Pacijentima se u praksi često
nudi odgovarajuća generička zamena, pri kojoj od koristi mogu biti informacije o BE između
generika, naročito u slučaju kada postoji sumnja da zamena generika može potencijalno
predstavljati rizik za pacijenta. Ove informacije mogu se dobiti procenom BE između
generičkih lekova metodom prilagođenog indirektnog poređenja, na osnovu podataka iz već
sprovedenih individualnih studija BE u kojima su generički lekovi poređeni sa istim
referentnim lekom. Na taj način identifikuju se generički lekovi za koje se prilikom zamene u
praksi ne očekuju problemi u pogledu efikasnosti i bezbednosti (1,2). Navedena metoda
korišćena je za poređenje četiri generička leka koji sadrže klopidogrel. Analizirani su javno
dostupni podaci iz studija BE u kojima je svaki generički lek poređen sa referentnim lekom
Plavix film tablete 75 mg. Dva generička leka smatraju se BE ukoliko je 90% interval
pouzdanosti (CI) za odnos njihovih farmakokinetičkih parametara maksimalna koncenracija
u plazmi (C max) i površina ispod krive do poslednje merljive koncentracije (PIK 0-t ), unutar
raspona 80,00-125,00%. U svim ispitanim kombinacijama 90% CI za PIK0-t bili su unutar
dozvoljenog raspona, dok su 90% CI za Cmax bili unutar ili veoma blizu granica ovog raspona,
pri čemu je point estimate u svim slučajevima bio unutar raspona. Rezultati dobijeni
metodom prilagođenog indirektnog poređenja pokazali su da je biološka raspoloživost ova
četiri generička leka koja sadrže klopidogrel veoma slična, te se oni mogu smatrati
međusobno zamenjivim u kliničkoj praksi.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel
T1  - Primena metode prilagođenog indirektnog poređenja u proceni biološke ekvivalnetnosti i zamenjivosti generičkih lekova – primer klopidogrela
VL  - 72
IS  - 4 suplement
SP  - S262
EP  - S263
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4526
ER  - 

@conference{
author = "Pejčić, Zorica and Vučićević, Katarina and García Arieta, Alfredo and Miljković, Branislava",
year = "2022",
abstract = "Generic medicines are bioequivalent (BE) and switchable with the reference medicine,
however, between generics BE is not demonstrated. In practice, patients are often offered
generic substitution, where information on BE between generics may be useful, especially
when there is a doubt that substitution may potentially pose a risk to the patient. These
information can be obtained by assessing BE between generics, applying the method of
adjusted indirect comparison (AIC). This method is based on data from BE studies in which
generics were compared with the same reference medicine. Thus, it is possible to identify
generics for which efficacy and safety problems are not expected upon substitution (1,2).
The AIC was used to compare four generic clopidogrel medicines. Publicly available data
from original BE studies, in which each generic medicine was compared with the reference
medicine Plavix film-coated tablets 75 mg, were analysed. Generics were considered BE if the
90% confidence interval (CI) for the ratio of their pharmacokinetic parameters maximum
plasma concentration (Cmax) and area under the curve up to the last measurable
concentration (PIK 0-t), was within the acceptance range 80.00-125.00%. In all the tested
combinations, 90% CIs for PIK0-t were within the acceptance range, while for C max 90% CIs
were within or very close to the limits, with the point estimate being within the range in all
cases. The results obtained by the AIC indicated that the bioavailability of these four generic
clopidogrel medicines is very similar, therefore they can be considered switchable with each
other in clinical practice., Generički lekovi su biološki ekvivalentni (BE) i zamenjivi sa referentnim lekom,
međutim, između samih generičkih lekova BE nije potvrđena. Pacijentima se u praksi često
nudi odgovarajuća generička zamena, pri kojoj od koristi mogu biti informacije o BE između
generika, naročito u slučaju kada postoji sumnja da zamena generika može potencijalno
predstavljati rizik za pacijenta. Ove informacije mogu se dobiti procenom BE između
generičkih lekova metodom prilagođenog indirektnog poređenja, na osnovu podataka iz već
sprovedenih individualnih studija BE u kojima su generički lekovi poređeni sa istim
referentnim lekom. Na taj način identifikuju se generički lekovi za koje se prilikom zamene u
praksi ne očekuju problemi u pogledu efikasnosti i bezbednosti (1,2). Navedena metoda
korišćena je za poređenje četiri generička leka koji sadrže klopidogrel. Analizirani su javno
dostupni podaci iz studija BE u kojima je svaki generički lek poređen sa referentnim lekom
Plavix film tablete 75 mg. Dva generička leka smatraju se BE ukoliko je 90% interval
pouzdanosti (CI) za odnos njihovih farmakokinetičkih parametara maksimalna koncenracija
u plazmi (C max) i površina ispod krive do poslednje merljive koncentracije (PIK 0-t ), unutar
raspona 80,00-125,00%. U svim ispitanim kombinacijama 90% CI za PIK0-t bili su unutar
dozvoljenog raspona, dok su 90% CI za Cmax bili unutar ili veoma blizu granica ovog raspona,
pri čemu je point estimate u svim slučajevima bio unutar raspona. Rezultati dobijeni
metodom prilagođenog indirektnog poređenja pokazali su da je biološka raspoloživost ova
četiri generička leka koja sadrže klopidogrel veoma slična, te se oni mogu smatrati
međusobno zamenjivim u kliničkoj praksi.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel, Primena metode prilagođenog indirektnog poređenja u proceni biološke ekvivalnetnosti i zamenjivosti generičkih lekova – primer klopidogrela",
volume = "72",
number = "4 suplement",
pages = "S262-S263",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4526"
}

Pejčić, Z., Vučićević, K., García Arieta, A.,& Miljković, B.. (2022). Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S262-S263.
https://hdl.handle.net/21.15107/rcub_farfar_4526

Pejčić Z, Vučićević K, García Arieta A, Miljković B. Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel. in Arhiv za farmaciju. 2022;72(4 suplement):S262-S263.
https://hdl.handle.net/21.15107/rcub_farfar_4526 .

Pejčić, Zorica, Vučićević, Katarina, García Arieta, Alfredo, Miljković, Branislava, "Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S262-S263,
https://hdl.handle.net/21.15107/rcub_farfar_4526 .

TY  - CONF
AU  - Homšek, Ana
AU  - Jovanović, Marija
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4508
AB  - Monoclonal antibodies’ pharmacokinetics is, due to their specific properties, highly
variable among different patients. Beside body weight and albumin levels, pembrolizumab
pharmacokinetics may also be affected by patient's condition depicted as ECOG (Eastern
Cooperative Oncology Group) performance status and tumor burden. The study aim was to
compare pembrolizumab exposure in different patient subpopulations after administration
of fixed (200 mg) and weight-based dosing regimen (2 mg/kg) every three weeks. Two
virtual populations were generated in the R software: normal body weight patients with
preserved renal function, normal albumin levels (3.4-5.8 g/dL) and good prognosis (ECOG 0,
low burden); and underweight patients with decreased renal function, hypoalbuminemia
(<3.4 g/dL) and poor prognosis (ECOG 1, high burden). The simulation was performed using
an already developed two-compartment covariate model. Drug exposure is expected to be
higher in the underweight group after the fixed dose administration compared to normal
patients. As for weight-based administration, equivalent drug exposure was observed in both
groups, as reduced clearance in the underweight group leads to similar drug concentrations.
In the group of normal patients, no significant difference was observed between the two
proposed dosing methods. Based on the conducted simulation, it is expected that all patients,
regardless of the dosing method, will have exposures to pembrolizumab that provide
effective treatment. Since the use of a fixed dose is more cost-effective, and increased
pembrolizumab exposure in underweight patients with poor prognosis could lead to adverse
reactions, therapeutic-drug-monitoring-based dosing should be considered in such patients.
AB  - Farmakokinetika monoklonskih antitela je, zbog njihovih specifičnih svojstava, veoma
varijabilna među različitim pacijentima. Pored uticaja telesne mase i nivoa albumina,
pretpostavlja se da na farmakokinetiku pembrolizumaba može uticati i stanje pacijenta
okarakterisano ECOG (Eastern Cooperative Oncology Group) performans statusom i
opterećenjem tumorom. Cilj ovog istraživanja bio je da se uporedi izloženost
pembrolizumabu u različitim subpopulacijama pacijenata nakon primene fiksnog (200 mg) i
režima doziranja po kilogramu telesne mase (2 mg/kg) svake tri nedelje. Upotrebom
softvera R generisane su dve virtuelne populacije: pacijenti normalne telesne mase sa
očuvanom bubrežnom funkcijom, normalnim nivoom albumina (3,4-5,8 g/dL) i dobrom
prognozom (ECOG 0, nisko opterećenje); i pothranjeni pacijenti sa smanjenom bubrežnom
funkcijom, hipoalbuminemiom (< 3,4 g/dL) i lošom prognozom (ECOG 1, visoko
opterećenje). Simulacija je urađena pomoću već razvijenog dvoprostornog modela sa
kovarijatama. Izloženost leku očekivano je veća u grupi pothranjenih pacijenata prilikom
primene fiksne doze u odnosu na normalne pacijente. Kada je u pitanju primena po telesnoj
masi, ekvivalentna izloženost leku primećena je u obe grupe, pošto smanjen klirens u grupi
pothranjenih dovodi do postizanja sličnih koncentracija leka. U grupi normalnih pacijenata
nije primećena značajna razlika između dva predložena načina doziranja.Na osnovu
sprovedene simulacije očekuje se da kod svih pacijenata, bez obzira na način doziranja, bude
postignuta izloženost leku koja obezbeđuje efikasnu terapiju. Kako je primena fiksne doze
isplativija, a povećana izloženost pembrolizumabu kod pothranjenih pacijenata sa lošom
prognozom može dovesti do pojave neželjenih reakcija, potrebno je kod ovakvih pacijenata
razmotriti doziranje bazirano na terapijskom monitoringu.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation
T1  - Procena izloženosti pembrolizumabu u različitim subpopulacijama pacijenata upotrebom farmakometrijske simulacije
VL  - 72
IS  - 4 suplement
SP  - S227
EP  - S228
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4508
ER  - 

@conference{
author = "Homšek, Ana and Jovanović, Marija and Miljković, Branislava and Vučićević, Katarina",
year = "2022",
abstract = "Monoclonal antibodies’ pharmacokinetics is, due to their specific properties, highly
variable among different patients. Beside body weight and albumin levels, pembrolizumab
pharmacokinetics may also be affected by patient's condition depicted as ECOG (Eastern
Cooperative Oncology Group) performance status and tumor burden. The study aim was to
compare pembrolizumab exposure in different patient subpopulations after administration
of fixed (200 mg) and weight-based dosing regimen (2 mg/kg) every three weeks. Two
virtual populations were generated in the R software: normal body weight patients with
preserved renal function, normal albumin levels (3.4-5.8 g/dL) and good prognosis (ECOG 0,
low burden); and underweight patients with decreased renal function, hypoalbuminemia
(<3.4 g/dL) and poor prognosis (ECOG 1, high burden). The simulation was performed using
an already developed two-compartment covariate model. Drug exposure is expected to be
higher in the underweight group after the fixed dose administration compared to normal
patients. As for weight-based administration, equivalent drug exposure was observed in both
groups, as reduced clearance in the underweight group leads to similar drug concentrations.
In the group of normal patients, no significant difference was observed between the two
proposed dosing methods. Based on the conducted simulation, it is expected that all patients,
regardless of the dosing method, will have exposures to pembrolizumab that provide
effective treatment. Since the use of a fixed dose is more cost-effective, and increased
pembrolizumab exposure in underweight patients with poor prognosis could lead to adverse
reactions, therapeutic-drug-monitoring-based dosing should be considered in such patients., Farmakokinetika monoklonskih antitela je, zbog njihovih specifičnih svojstava, veoma
varijabilna među različitim pacijentima. Pored uticaja telesne mase i nivoa albumina,
pretpostavlja se da na farmakokinetiku pembrolizumaba može uticati i stanje pacijenta
okarakterisano ECOG (Eastern Cooperative Oncology Group) performans statusom i
opterećenjem tumorom. Cilj ovog istraživanja bio je da se uporedi izloženost
pembrolizumabu u različitim subpopulacijama pacijenata nakon primene fiksnog (200 mg) i
režima doziranja po kilogramu telesne mase (2 mg/kg) svake tri nedelje. Upotrebom
softvera R generisane su dve virtuelne populacije: pacijenti normalne telesne mase sa
očuvanom bubrežnom funkcijom, normalnim nivoom albumina (3,4-5,8 g/dL) i dobrom
prognozom (ECOG 0, nisko opterećenje); i pothranjeni pacijenti sa smanjenom bubrežnom
funkcijom, hipoalbuminemiom (< 3,4 g/dL) i lošom prognozom (ECOG 1, visoko
opterećenje). Simulacija je urađena pomoću već razvijenog dvoprostornog modela sa
kovarijatama. Izloženost leku očekivano je veća u grupi pothranjenih pacijenata prilikom
primene fiksne doze u odnosu na normalne pacijente. Kada je u pitanju primena po telesnoj
masi, ekvivalentna izloženost leku primećena je u obe grupe, pošto smanjen klirens u grupi
pothranjenih dovodi do postizanja sličnih koncentracija leka. U grupi normalnih pacijenata
nije primećena značajna razlika između dva predložena načina doziranja.Na osnovu
sprovedene simulacije očekuje se da kod svih pacijenata, bez obzira na način doziranja, bude
postignuta izloženost leku koja obezbeđuje efikasnu terapiju. Kako je primena fiksne doze
isplativija, a povećana izloženost pembrolizumabu kod pothranjenih pacijenata sa lošom
prognozom može dovesti do pojave neželjenih reakcija, potrebno je kod ovakvih pacijenata
razmotriti doziranje bazirano na terapijskom monitoringu.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation, Procena izloženosti pembrolizumabu u različitim subpopulacijama pacijenata upotrebom farmakometrijske simulacije",
volume = "72",
number = "4 suplement",
pages = "S227-S228",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4508"
}

Homšek, A., Jovanović, M., Miljković, B.,& Vučićević, K.. (2022). Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S227-S228.
https://hdl.handle.net/21.15107/rcub_farfar_4508

Homšek A, Jovanović M, Miljković B, Vučićević K. Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation. in Arhiv za farmaciju. 2022;72(4 suplement):S227-S228.
https://hdl.handle.net/21.15107/rcub_farfar_4508 .

Homšek, Ana, Jovanović, Marija, Miljković, Branislava, Vučićević, Katarina, "Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S227-S228,
https://hdl.handle.net/21.15107/rcub_farfar_4508 .

TY  - CONF
AU  - Panić, Bojana
AU  - Jovanović, Marija
AU  - Lukić, Vera
AU  - Bulat, Zorica
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
AU  - Milovanović, Srđan
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4507
AB  - The atypical antipsychotic clozapine (CLZ) is primarily used for the treatment-
resistant schizophrenia. Due to low therapeutic index and high pharmacokinetic variability,
therapeutic drug monitoring (TDM) is highly recommended (1). The aim of this retrospective
study was to analyze TDM data of CLZ and its active metabolite norclozapine (NCLZ) in adult
patient with schizophrenia. The study included CLZ TDM data obtained from 69 patients (22-
67 years) treated at the Clinic for Psychiatry, Clinical Center of Serbia, while NCLZ data were
available from 43 patients. Serum concentrations were determined at the Institute of
Forensic Medicine, Belgrade, Serbia using liquid chromatography with tandem mass
spectrometry (LC‐MS/MS). Statistical analysis was performed by SPSS software® (version
18). The daily doses of CLZ ranged between 37.5 and 600 mg. The mean value of CLZ and
NCLZ levels were 0.285 ± 0.174 mg/L and 0.189 ± 0.132 mg/L, respectively. 73.06% and
26.83% of measured CLZ and NCLZ concentrations were outside reference range (mostly
below), respectively. Significant positive correlation (p<0.05) was observed between daily
dose and CLZ levels, as well as between dose and NCLZ levels. Significant correlations of dose
and CLZ levels were confirmed in males and females, smokers and nonsmokers, separately.
Parent drug and metabolite levels varied 13 and 16-fold in patients receiving 300 mg/day,
respectively. The results indicate considerable variability in CLZ and NCLZ concentrations in
adult patients with schizophrenia, and positive association with dose. Further multivariate
analysis is required to assess, in addition to dose, potential influences of other patient and
co-therapy factors.
AB  - Atipični antipsihotik klozapin (clozapine, CLZ) se primarno koristi kod shizofrenije
rezistentne na terapiju. Zbog niskog terapijskog indeksa i velike farmakokinetičke
varijabilnosti, terapijsko prać enje lekova (therapeutic drug monitoring, TDM) se preporučuje
(1). Cilj ovog retrospektivnog istraživanja je bio ispitivanje TDM podataka o CLZ i njegovom
aktivnom metabolitu norklozapinu (norclozapine, NCLZ) kod odraslih pacijenata sa
shizofrenijom. Studija je obuhvatila TDM podatke o CLZ dobijene od 69 pacijenata (22-67
godina) lečenih na Klinici za psihijatriju Kliničkog centra Srbije, dok su podaci za NCLZ bili
dostupni od 43 pacijenta. Koncentracije u serumu su merene na Institutu za sudsku
medicinu, Beograd, Srbija tečnom hromatografijom sa tandem masenom spektrometrijom
(LC‐MS/MS). Statistička analiza je izvršena pomoć u softvera SPSS® (verzija 18). Dnevne doze
CLZ kretale su se između 37,5 i 600 mg. Srednja vrednost je bila 0,285 ± 0,174 mg/L za CLZ i
0,189 ± 0,132 mg/L za NCLZ. 73,06% i 26,83% izmerenih koncentracija CLZ i NCLZ bile su
izvan referentnog opsega (uglavnom ispod), respektivno. Detektovana je pozitivna korelacija
(p<0,05) između dnevne doze i nivoa CLZ, kao i doze i nivoa NCLZ. Značajna korelacija doze i
nivoa CLZ je potvrđena i pri odvojenom ispitivanju kod muškaraca, žena, pušača i nepušača.
Nivoi leka i metabolita varirali su 13 i 16 puta kod pacijenata koji su uzimali 300 mg/dan,
respektivno. Rezultati ukazuju na značajnu varijabilnost u koncentracijama CLZ i NCLZ kod
odraslih pacijenata sa shizofrenijom i pozitivnu povezanost sa dozom. Potrebna je dalja
multivarijantna analiza da bi se procenili, pored doze, potencijalni uticaji karakteristika
pacijenata i kombinovane terapije.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia
T1  - Analiza koncentracija klozapina i norklozapina kod odraslih pacijenata sa shizofrenijom
VL  - 72
IS  - 4 suplement
SP  - S225
EP  - S226
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4507
ER  - 

@conference{
author = "Panić, Bojana and Jovanović, Marija and Lukić, Vera and Bulat, Zorica and Vučićević, Katarina and Miljković, Branislava and Milovanović, Srđan",
year = "2022",
abstract = "The atypical antipsychotic clozapine (CLZ) is primarily used for the treatment-
resistant schizophrenia. Due to low therapeutic index and high pharmacokinetic variability,
therapeutic drug monitoring (TDM) is highly recommended (1). The aim of this retrospective
study was to analyze TDM data of CLZ and its active metabolite norclozapine (NCLZ) in adult
patient with schizophrenia. The study included CLZ TDM data obtained from 69 patients (22-
67 years) treated at the Clinic for Psychiatry, Clinical Center of Serbia, while NCLZ data were
available from 43 patients. Serum concentrations were determined at the Institute of
Forensic Medicine, Belgrade, Serbia using liquid chromatography with tandem mass
spectrometry (LC‐MS/MS). Statistical analysis was performed by SPSS software® (version
18). The daily doses of CLZ ranged between 37.5 and 600 mg. The mean value of CLZ and
NCLZ levels were 0.285 ± 0.174 mg/L and 0.189 ± 0.132 mg/L, respectively. 73.06% and
26.83% of measured CLZ and NCLZ concentrations were outside reference range (mostly
below), respectively. Significant positive correlation (p<0.05) was observed between daily
dose and CLZ levels, as well as between dose and NCLZ levels. Significant correlations of dose
and CLZ levels were confirmed in males and females, smokers and nonsmokers, separately.
Parent drug and metabolite levels varied 13 and 16-fold in patients receiving 300 mg/day,
respectively. The results indicate considerable variability in CLZ and NCLZ concentrations in
adult patients with schizophrenia, and positive association with dose. Further multivariate
analysis is required to assess, in addition to dose, potential influences of other patient and
co-therapy factors., Atipični antipsihotik klozapin (clozapine, CLZ) se primarno koristi kod shizofrenije
rezistentne na terapiju. Zbog niskog terapijskog indeksa i velike farmakokinetičke
varijabilnosti, terapijsko prać enje lekova (therapeutic drug monitoring, TDM) se preporučuje
(1). Cilj ovog retrospektivnog istraživanja je bio ispitivanje TDM podataka o CLZ i njegovom
aktivnom metabolitu norklozapinu (norclozapine, NCLZ) kod odraslih pacijenata sa
shizofrenijom. Studija je obuhvatila TDM podatke o CLZ dobijene od 69 pacijenata (22-67
godina) lečenih na Klinici za psihijatriju Kliničkog centra Srbije, dok su podaci za NCLZ bili
dostupni od 43 pacijenta. Koncentracije u serumu su merene na Institutu za sudsku
medicinu, Beograd, Srbija tečnom hromatografijom sa tandem masenom spektrometrijom
(LC‐MS/MS). Statistička analiza je izvršena pomoć u softvera SPSS® (verzija 18). Dnevne doze
CLZ kretale su se između 37,5 i 600 mg. Srednja vrednost je bila 0,285 ± 0,174 mg/L za CLZ i
0,189 ± 0,132 mg/L za NCLZ. 73,06% i 26,83% izmerenih koncentracija CLZ i NCLZ bile su
izvan referentnog opsega (uglavnom ispod), respektivno. Detektovana je pozitivna korelacija
(p<0,05) između dnevne doze i nivoa CLZ, kao i doze i nivoa NCLZ. Značajna korelacija doze i
nivoa CLZ je potvrđena i pri odvojenom ispitivanju kod muškaraca, žena, pušača i nepušača.
Nivoi leka i metabolita varirali su 13 i 16 puta kod pacijenata koji su uzimali 300 mg/dan,
respektivno. Rezultati ukazuju na značajnu varijabilnost u koncentracijama CLZ i NCLZ kod
odraslih pacijenata sa shizofrenijom i pozitivnu povezanost sa dozom. Potrebna je dalja
multivarijantna analiza da bi se procenili, pored doze, potencijalni uticaji karakteristika
pacijenata i kombinovane terapije.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia, Analiza koncentracija klozapina i norklozapina kod odraslih pacijenata sa shizofrenijom",
volume = "72",
number = "4 suplement",
pages = "S225-S226",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4507"
}

Panić, B., Jovanović, M., Lukić, V., Bulat, Z., Vučićević, K., Miljković, B.,& Milovanović, S.. (2022). Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S225-S226.
https://hdl.handle.net/21.15107/rcub_farfar_4507

Panić B, Jovanović M, Lukić V, Bulat Z, Vučićević K, Miljković B, Milovanović S. Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia. in Arhiv za farmaciju. 2022;72(4 suplement):S225-S226.
https://hdl.handle.net/21.15107/rcub_farfar_4507 .

Panić, Bojana, Jovanović, Marija, Lukić, Vera, Bulat, Zorica, Vučićević, Katarina, Miljković, Branislava, Milovanović, Srđan, "Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S225-S226,
https://hdl.handle.net/21.15107/rcub_farfar_4507 .

TY  - CONF
AU  - Jovanović, Marija
AU  - Ćulafić, Milica
AU  - Pejić, Nina
AU  - Štulić, Miloš
AU  - Kovačević, Milena
AU  - Vezmar-Kovačević, Sandra
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
AU  - Ćulafić, Đorđe
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4395
AB  - Takrolimus je imunosupresiv koji se primenjuje za prevenciju odbacivanja grafta
nakon transplantacije jetre. Uzak terapijski opseg i velika varijabilnost u farmakokinetici
ukazuju na neophodnost individualizacije terapije. Cilj istraživanja bio je razvoj i validacija
osnovnog farmakokinetičkog modela takrolimusa baziranog na podacima prikupljenim
tokom terapijskog praćenja leka. Studija je uključila 29 pacijenata sa transplantiranom
jetrom, praćenih na Klinici za gastroenterologiju i hepatologiju, Kliničkog centra Srbije.
Primenom NONMEM® programa analizirane su koncentracije takrolimusa izmerene u punoj
krvi (260), neposredno pre primene jutarnje doze (Ctrough). Farmakokinetika je opisana
jednoprostornim modelom sa resorpcijom i eliminacijom prvog reda. Interna validacija je
vršena primenom grafičke metode procene, metode umnožavanja podataka (bootstrap) i
vizuelne prediktivne provere (VPC). Procenjena tipična vrednost oralnog klirensa (CL/F)
iznosila je 30,4 L/h, dok je vrednost oralnog volumena distribucije bila 5770 L. Vrednost
konstante brzine resorpcije je fiksirana na 4,48 h-1 . Interindividualna varijabilnost je najbolje
opisana eksponencijalnim modelom, a rezidualna aditivnim modelom. Zabeležena je
interindividualna varijabilnost za CL/F od 38,2%. Predviđene individualne koncentracije
(IPRED) pokazuju bolje slaganje sa izmerenim vrednostima, nego populacione predviđene
vrednosti (PRED). Uslovni težinski reziduali (CWRES vs PRED, CWRES vs TIME) su većinom
raspoređeni između -2 i +2 standardne devijacije. Parametri dobijeni bootstrap analizom ne
odstupaju značajno od modela, dok su vrednosti medijane, 5. i 95. percentila u VPC metodi
uglavnom bile u okviru simuliranih 95% intervala pouzdanosti. Dobijeni populacioni
farmakokinetički model, može se nakon dodatne optimizacije, primeniti u svrhu
individualizacije režima doziranja takrolimusa u populaciji pacijenata sa transplantiranom
jetrom.
AB  - Tacrolimus is an immunosuppressant used to prevent graft rejection after liver transplantation. The narrow therapeutic range and great variability in pharmacokinetics indicate the need for therapy individualization. The aim of the study was to develop and validate the base pharmacokinetic model of tacrolimus using data collected during therapeutic drug monitoring. The study included 29 liver transplant recipients followed up at Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. Using the NONMEM® program, we analyzed tacrolimus concentrations (Ctrough) measured in whole blood (260). Pharmacokinetics have been described as one-compartment model with first- order absorption and elimination. Internal validation was performed using graphical assessment, bootstrap method and visual predictive check (VPC). Typical value of oral clearance (CL/F) was 30.4 L/h, while value of oral volume of distribution was 5770 L. The value of the absorption rate constant was fixed at 4.48 h-1 . Interindividual variability was best described by the exponential model, and residual by the additive model. Interindividual variability for CL/F was 38.2%. Individual predicted concentrations (IPRED) showed better agreement with the measured values than population predicted values (PRED). Conditional weighted residuals (CWRES vs PRED, CWRES vs TIME) were mostly between -2 and +2 standard deviations. The parameters obtained by bootstrap analysis do not deviate significantly from the model. Median, 5th and 95th percentiles in the VPC method mostly were within the simulated 95% confidence interval. The obtained population pharmacokinetic model, after additional optimization, can be used for individualization of the tacrolimus dosing regimen in the population of liver transplant recipients.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom
T1  - A population pharmacokinetic model of tacrolimus in adult liver transplant recipients
VL  - 72
IS  - 4 Suplement
SP  - S298
EP  - S299
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4395
ER  - 

@conference{
author = "Jovanović, Marija and Ćulafić, Milica and Pejić, Nina and Štulić, Miloš and Kovačević, Milena and Vezmar-Kovačević, Sandra and Miljković, Branislava and Vučićević, Katarina and Ćulafić, Đorđe",
year = "2022",
abstract = "Takrolimus je imunosupresiv koji se primenjuje za prevenciju odbacivanja grafta
nakon transplantacije jetre. Uzak terapijski opseg i velika varijabilnost u farmakokinetici
ukazuju na neophodnost individualizacije terapije. Cilj istraživanja bio je razvoj i validacija
osnovnog farmakokinetičkog modela takrolimusa baziranog na podacima prikupljenim
tokom terapijskog praćenja leka. Studija je uključila 29 pacijenata sa transplantiranom
jetrom, praćenih na Klinici za gastroenterologiju i hepatologiju, Kliničkog centra Srbije.
Primenom NONMEM® programa analizirane su koncentracije takrolimusa izmerene u punoj
krvi (260), neposredno pre primene jutarnje doze (Ctrough). Farmakokinetika je opisana
jednoprostornim modelom sa resorpcijom i eliminacijom prvog reda. Interna validacija je
vršena primenom grafičke metode procene, metode umnožavanja podataka (bootstrap) i
vizuelne prediktivne provere (VPC). Procenjena tipična vrednost oralnog klirensa (CL/F)
iznosila je 30,4 L/h, dok je vrednost oralnog volumena distribucije bila 5770 L. Vrednost
konstante brzine resorpcije je fiksirana na 4,48 h-1 . Interindividualna varijabilnost je najbolje
opisana eksponencijalnim modelom, a rezidualna aditivnim modelom. Zabeležena je
interindividualna varijabilnost za CL/F od 38,2%. Predviđene individualne koncentracije
(IPRED) pokazuju bolje slaganje sa izmerenim vrednostima, nego populacione predviđene
vrednosti (PRED). Uslovni težinski reziduali (CWRES vs PRED, CWRES vs TIME) su većinom
raspoređeni između -2 i +2 standardne devijacije. Parametri dobijeni bootstrap analizom ne
odstupaju značajno od modela, dok su vrednosti medijane, 5. i 95. percentila u VPC metodi
uglavnom bile u okviru simuliranih 95% intervala pouzdanosti. Dobijeni populacioni
farmakokinetički model, može se nakon dodatne optimizacije, primeniti u svrhu
individualizacije režima doziranja takrolimusa u populaciji pacijenata sa transplantiranom
jetrom., Tacrolimus is an immunosuppressant used to prevent graft rejection after liver transplantation. The narrow therapeutic range and great variability in pharmacokinetics indicate the need for therapy individualization. The aim of the study was to develop and validate the base pharmacokinetic model of tacrolimus using data collected during therapeutic drug monitoring. The study included 29 liver transplant recipients followed up at Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. Using the NONMEM® program, we analyzed tacrolimus concentrations (Ctrough) measured in whole blood (260). Pharmacokinetics have been described as one-compartment model with first- order absorption and elimination. Internal validation was performed using graphical assessment, bootstrap method and visual predictive check (VPC). Typical value of oral clearance (CL/F) was 30.4 L/h, while value of oral volume of distribution was 5770 L. The value of the absorption rate constant was fixed at 4.48 h-1 . Interindividual variability was best described by the exponential model, and residual by the additive model. Interindividual variability for CL/F was 38.2%. Individual predicted concentrations (IPRED) showed better agreement with the measured values than population predicted values (PRED). Conditional weighted residuals (CWRES vs PRED, CWRES vs TIME) were mostly between -2 and +2 standard deviations. The parameters obtained by bootstrap analysis do not deviate significantly from the model. Median, 5th and 95th percentiles in the VPC method mostly were within the simulated 95% confidence interval. The obtained population pharmacokinetic model, after additional optimization, can be used for individualization of the tacrolimus dosing regimen in the population of liver transplant recipients.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom, A population pharmacokinetic model of tacrolimus in adult liver transplant recipients",
volume = "72",
number = "4 Suplement",
pages = "S298-S299",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4395"
}

Jovanović, M., Ćulafić, M., Pejić, N., Štulić, M., Kovačević, M., Vezmar-Kovačević, S., Miljković, B., Vučićević, K.,& Ćulafić, Đ.. (2022). Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 Suplement), S298-S299.
https://hdl.handle.net/21.15107/rcub_farfar_4395

Jovanović M, Ćulafić M, Pejić N, Štulić M, Kovačević M, Vezmar-Kovačević S, Miljković B, Vučićević K, Ćulafić Đ. Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom. in Arhiv za farmaciju. 2022;72(4 Suplement):S298-S299.
https://hdl.handle.net/21.15107/rcub_farfar_4395 .

Jovanović, Marija, Ćulafić, Milica, Pejić, Nina, Štulić, Miloš, Kovačević, Milena, Vezmar-Kovačević, Sandra, Miljković, Branislava, Vučićević, Katarina, Ćulafić, Đorđe, "Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom" in Arhiv za farmaciju, 72, no. 4 Suplement (2022):S298-S299,
https://hdl.handle.net/21.15107/rcub_farfar_4395 .

TY  - CONF
AU  - Marković, Aleksandra
AU  - Kovačević, Milena
AU  - Ćulafić, Milica
AU  - Roganović, Maša
AU  - Jovanović, Marija
AU  - Vezmar-Kovačević, Sandra
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4391
AB  - Hronična opstruktivna bolest pluća (HOBP) je oboljenje sa visokom prevalencom koje
karakteriše progresivna, ireverzibilna opstrukcija disajnih puteva često udružena sa
pojačanim inflamatornim odgovorom. Simptomi dispneje, kašlja i umora mogu negativno
uticati na kvalitet života obolelih. HOBP je često udružen sa drugim hroničnim bolestima što
doprinosi njegovom morbiditetu i mortalitetu. Cilj ovog istraživanja je procena terapije u
lečenju HOBP i pridruženih komorbiditeta. Sprovedena je opservaciona studija koja je
uključila pacijente koji su dolazili u javne apoteke da preuzmu lek na recept za lečenje HOBP.
Podaci o pacijentima su prikupljeni popunjavanjem upitnika. Deskriptivna analiza urađena je
u programu Microsoft ® Office Excel 2010. U istraživanje je uključeno 82 ispitanika, od kojih
su brojniji bili muškarci (56,1%). Prosečna starost ispitanika iznosila je 66,1±10,6, sa
prosečnim trajanjem bolesti 10,2±3,8 godina. Najveći broj (89%) primenjivao je
kombinovane inhalacione preparate (antiholinergik+β-agonista), antiholinergik 46,3%,
salbutamol 24,4%, teofilin/aminofilin 26,9%, inhalacioni kortikosteroid 11.0%, antibiotike
14,6% i oralne kortikosteroide 4,9%. Čak 97,6% pacijenata imao je pridruženu hroničnu
bolest - broj komorbiditeta po pacijentu 1-5. U 73,8% slučajeva je u pitanju hipertenzija,
21,3% imalo je astmu, i 12,2% dijabetes ili srčanu slabost. Primenom mMRC (modified
Medical Research Council) skale za procenu dispneje, vrednosti ≥2 imalo je 53,7% ispitanika
što ukazuje na slabo kontrolisanu bolest. Skoro četvrtina pacijenata bila je hospitalizovana
zbog egzacerbacije (23,2%), 53,7% vakcinisano protiv gripa, a samo 3,7% protiv
pneumokoka. Oko trećina ispitanika bili su pušači (35,4%). Uzimajući u obzir zastupljenost
komorbiditeta u ovoj populaciji i složenost terapije, savetovanje i praćenje od strane
farmaceuta moglo bi značajno doprineti sprečavanju potencijalnih terapijskih problema.
AB  - Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease
characterized by progressive, irreversible airway obstruction often associated with
increased inflammatory response. Symptoms including dyspnea, cough and fatigue can
negatively affect patients’ quality of life. COPD is often associated with other chronic diseases
that contribute to its morbidity and mortality. The aim of this research was to evaluate the
therapy of COPD and comorbidities. An observational study included patients with a
prescription for COPD medications. Patients’ data were collected by completing
questionnaires in the community pharmacies. Descriptive analysis was performed in
Microsoft® Office Excel 2010. Among 82 participants most of them were men (56.1%).
Participants’ average age was 66.1±10.6 with an average disease duration of 10.2±3.8 years.
Most participants (89%) used combined inhalation preparations (anticholinergic+β-agonist),
anticholinergic 46.3%, salbutamol 24.4%, theophylline/aminophylline 26.9%, inhaled
corticosteroid 11.0%, antibiotics 14.6% and oral corticosteroids 4.9%. Additional chronic
disease was present in 97.6% of patients, with 1-5 comorbidities per patient. The majority of
patients also had hypertension 73.8%, 21.3% asthma and 12.2% diabetes or heart failure.
Using the mMRC (modified Medical Research Council) scale for the assessment of dyspnea,
53.7% had a score ≥2, indicating a poorly controlled disease. Almost a quarter of patients
were hospitalized for exacerbation (23.2%), 53.7% were vaccinated against influenza, only
3.7% against pneumococcus and about a third were smokers (35.4%). Given the prevalence
of comorbidities in this population and the complexity of therapy, counseling and monitoring
by pharmacists could make a significant contribution to preventing potential drug-related
problems.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća
T1  - Assessment of therapy and comorbidities in patients with chronic obstructive pulmonary disease
VL  - 72
IS  - 4-suplement
SP  - S282
EP  - S283
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4391
ER  - 

@conference{
author = "Marković, Aleksandra and Kovačević, Milena and Ćulafić, Milica and Roganović, Maša and Jovanović, Marija and Vezmar-Kovačević, Sandra and Vučićević, Katarina and Miljković, Branislava",
year = "2022",
abstract = "Hronična opstruktivna bolest pluća (HOBP) je oboljenje sa visokom prevalencom koje
karakteriše progresivna, ireverzibilna opstrukcija disajnih puteva često udružena sa
pojačanim inflamatornim odgovorom. Simptomi dispneje, kašlja i umora mogu negativno
uticati na kvalitet života obolelih. HOBP je često udružen sa drugim hroničnim bolestima što
doprinosi njegovom morbiditetu i mortalitetu. Cilj ovog istraživanja je procena terapije u
lečenju HOBP i pridruženih komorbiditeta. Sprovedena je opservaciona studija koja je
uključila pacijente koji su dolazili u javne apoteke da preuzmu lek na recept za lečenje HOBP.
Podaci o pacijentima su prikupljeni popunjavanjem upitnika. Deskriptivna analiza urađena je
u programu Microsoft ® Office Excel 2010. U istraživanje je uključeno 82 ispitanika, od kojih
su brojniji bili muškarci (56,1%). Prosečna starost ispitanika iznosila je 66,1±10,6, sa
prosečnim trajanjem bolesti 10,2±3,8 godina. Najveći broj (89%) primenjivao je
kombinovane inhalacione preparate (antiholinergik+β-agonista), antiholinergik 46,3%,
salbutamol 24,4%, teofilin/aminofilin 26,9%, inhalacioni kortikosteroid 11.0%, antibiotike
14,6% i oralne kortikosteroide 4,9%. Čak 97,6% pacijenata imao je pridruženu hroničnu
bolest - broj komorbiditeta po pacijentu 1-5. U 73,8% slučajeva je u pitanju hipertenzija,
21,3% imalo je astmu, i 12,2% dijabetes ili srčanu slabost. Primenom mMRC (modified
Medical Research Council) skale za procenu dispneje, vrednosti ≥2 imalo je 53,7% ispitanika
što ukazuje na slabo kontrolisanu bolest. Skoro četvrtina pacijenata bila je hospitalizovana
zbog egzacerbacije (23,2%), 53,7% vakcinisano protiv gripa, a samo 3,7% protiv
pneumokoka. Oko trećina ispitanika bili su pušači (35,4%). Uzimajući u obzir zastupljenost
komorbiditeta u ovoj populaciji i složenost terapije, savetovanje i praćenje od strane
farmaceuta moglo bi značajno doprineti sprečavanju potencijalnih terapijskih problema., Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease
characterized by progressive, irreversible airway obstruction often associated with
increased inflammatory response. Symptoms including dyspnea, cough and fatigue can
negatively affect patients’ quality of life. COPD is often associated with other chronic diseases
that contribute to its morbidity and mortality. The aim of this research was to evaluate the
therapy of COPD and comorbidities. An observational study included patients with a
prescription for COPD medications. Patients’ data were collected by completing
questionnaires in the community pharmacies. Descriptive analysis was performed in
Microsoft® Office Excel 2010. Among 82 participants most of them were men (56.1%).
Participants’ average age was 66.1±10.6 with an average disease duration of 10.2±3.8 years.
Most participants (89%) used combined inhalation preparations (anticholinergic+β-agonist),
anticholinergic 46.3%, salbutamol 24.4%, theophylline/aminophylline 26.9%, inhaled
corticosteroid 11.0%, antibiotics 14.6% and oral corticosteroids 4.9%. Additional chronic
disease was present in 97.6% of patients, with 1-5 comorbidities per patient. The majority of
patients also had hypertension 73.8%, 21.3% asthma and 12.2% diabetes or heart failure.
Using the mMRC (modified Medical Research Council) scale for the assessment of dyspnea,
53.7% had a score ≥2, indicating a poorly controlled disease. Almost a quarter of patients
were hospitalized for exacerbation (23.2%), 53.7% were vaccinated against influenza, only
3.7% against pneumococcus and about a third were smokers (35.4%). Given the prevalence
of comorbidities in this population and the complexity of therapy, counseling and monitoring
by pharmacists could make a significant contribution to preventing potential drug-related
problems.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća, Assessment of therapy and comorbidities in patients with chronic obstructive pulmonary disease",
volume = "72",
number = "4-suplement",
pages = "S282-S283",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4391"
}

Marković, A., Kovačević, M., Ćulafić, M., Roganović, M., Jovanović, M., Vezmar-Kovačević, S., Vučićević, K.,& Miljković, B.. (2022). Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4-suplement), S282-S283.
https://hdl.handle.net/21.15107/rcub_farfar_4391

Marković A, Kovačević M, Ćulafić M, Roganović M, Jovanović M, Vezmar-Kovačević S, Vučićević K, Miljković B. Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća. in Arhiv za farmaciju. 2022;72(4-suplement):S282-S283.
https://hdl.handle.net/21.15107/rcub_farfar_4391 .

Marković, Aleksandra, Kovačević, Milena, Ćulafić, Milica, Roganović, Maša, Jovanović, Marija, Vezmar-Kovačević, Sandra, Vučićević, Katarina, Miljković, Branislava, "Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća" in Arhiv za farmaciju, 72, no. 4-suplement (2022):S282-S283,
https://hdl.handle.net/21.15107/rcub_farfar_4391 .

TY  - CONF
AU  - Lazarević, Katarina
AU  - Kovačević, Milena
AU  - Ćulafić, Milica
AU  - Jovanović, Marija
AU  - Roganović, Maša
AU  - Vezmar-Kovačević, Sandra
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4390
AB  - Astma predstavlja veliko globalno opterećenje jer se uprkos dostupnoj terapiji beleže
loši zdravstveni i socio-ekonomski ishodi. Cilj ovog rada je analiza primenjene terapije i
koterapije kod pacijenata obolelih od astme i identifikacija terapijskih problema. Sprovedena
opservaciona studija je uključila 57 odraslih pacijenata sa astmom, oba pola. Podaci su
prikupljani tokom 2016. godine u javnim apotekama, popunjavanjem upitnika. Deskriptivna
analiza je izvršena u programu Microsoft ® Office Excel 2010. Prosečna starost iznosila je
49,7±17,4 godina, 38,6% činili su muškarci. Kratkodelujuće beta-2 agoniste primenjivalo je
36,8% pacijenata, dugodelujuće beta-2 agoniste 8,8%, inhalacione kortikosteroide 28,1%,
dok je kombinovane preparate upotrebljavalo 73,7%. Više od 50% koristilo je inhalacione
antiholinergike, a primećena je upotreba teofilina/aminofilina kod 31,6%, što nije u
saglasnosti sa smernicama za terapiju astme usled slabe efikasnosti, odnosno lošeg
bezbednosnog profila. Takođe, ovaj rezultat može ukazati na to da pacijenti ne prihvataju
inhalacionu terapiju zbog zahtevnijeg načina primene ili zbog više cene lekova. Od
pridruženih komorbiditeta, najčešći su bili alergijski rinitis, gojaznost, hipertenzija i
gastroezofagealna refluksna bolest. Potencijalno neadekvatna koterapija uključivala je beta-
blokatore (21,1%), inhibitore angiotenzin-konvertujućeg enzima (28,1%), acetilsalicilnu
kiselinu/nesteroidne antiinflamatorne lekove (21,1% i 29,8%) čija primena može
precipitirati pogoršanje astme. Obeshrabrujuće je da su 26,3% pacijenata pušači, 35,1% ne
zna koji su okidači za njihovu bolest, a samo 1 pacijent koristi astma akcioni plan. Rezultati
ukazuju na veću zastupljenost terapije koja odgovara težim stadijumima astme, što može
ukazivati na lošiju kontrolu bolesti i lošije ishode. Uočava se potreba za uvođenjem usluga
farmaceutske zdravstvene zaštite i boljom edukacijom pacijenata o astmi.
AB  - Asthma represents a serious global burden because, despite available therapy, poor
health and socio-economic outcomes are reported. The aim of this paper is to analyse
treatment in patients with asthma and to identify drug-related problems. An observational
study included 57 adult asthma patients of both genders. Data were collected in community
pharmacies during 2016, by filling out questionnaires. Descriptive analysis was performed in
Microsoft® Office Excel 2010. Respondents’ average age was 49.7±17.4, 38.6% were men.
Patients used short-acting (36.8%) and long-acting beta-2 agonists (8.8%), inhaled
corticosteroids (28.1%) and combined preparations (73.7%). More than 50% of patients
used inhaled anticholinergics, while theophylline was used in 31.6%, which is in discordance
with the asthma guidelines, due to poor efficacy and safety profile. Also, this may indicate
that patients do not accept inhalation therapy because of demanding technique or higher
cost. Allergic rhinitis, obesity, hypertension, and gastroesophageal reflux disease were the
most common comorbidities. Potentially inadequate co-therapy included beta-blockers
(21.1%), angiotensin-converting enzyme inhibitors (28.1%), aspirin/nonsteroidal
antiinflamatory drugs (21.1% and 29.8%), which may worsen asthma. It is discouraging that
26.3% of patients were smokers, 35.1% did not know the triggers for asthma, and only 1
patient used the asthma action plan. The results show a higher prevalence of therapy
appropriate for severe asthma stages, which implies poor disease control and poor
outcomes. There is a need for the implementation of pharmaceutical care services and better
education of patients with asthma.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Pregled terapije i terapijskih problema kod pacijenata sa astmom u primarnoj zdravstvenoj zaštiti
T1  - Review of therapy and therapeutic problems in patients with asthma in primary health care
VL  - 72
IS  - 4-suplement
SP  - S280
EP  - S281
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4390
ER  - 

@conference{
author = "Lazarević, Katarina and Kovačević, Milena and Ćulafić, Milica and Jovanović, Marija and Roganović, Maša and Vezmar-Kovačević, Sandra and Vučićević, Katarina and Miljković, Branislava",
year = "2022",
abstract = "Astma predstavlja veliko globalno opterećenje jer se uprkos dostupnoj terapiji beleže
loši zdravstveni i socio-ekonomski ishodi. Cilj ovog rada je analiza primenjene terapije i
koterapije kod pacijenata obolelih od astme i identifikacija terapijskih problema. Sprovedena
opservaciona studija je uključila 57 odraslih pacijenata sa astmom, oba pola. Podaci su
prikupljani tokom 2016. godine u javnim apotekama, popunjavanjem upitnika. Deskriptivna
analiza je izvršena u programu Microsoft ® Office Excel 2010. Prosečna starost iznosila je
49,7±17,4 godina, 38,6% činili su muškarci. Kratkodelujuće beta-2 agoniste primenjivalo je
36,8% pacijenata, dugodelujuće beta-2 agoniste 8,8%, inhalacione kortikosteroide 28,1%,
dok je kombinovane preparate upotrebljavalo 73,7%. Više od 50% koristilo je inhalacione
antiholinergike, a primećena je upotreba teofilina/aminofilina kod 31,6%, što nije u
saglasnosti sa smernicama za terapiju astme usled slabe efikasnosti, odnosno lošeg
bezbednosnog profila. Takođe, ovaj rezultat može ukazati na to da pacijenti ne prihvataju
inhalacionu terapiju zbog zahtevnijeg načina primene ili zbog više cene lekova. Od
pridruženih komorbiditeta, najčešći su bili alergijski rinitis, gojaznost, hipertenzija i
gastroezofagealna refluksna bolest. Potencijalno neadekvatna koterapija uključivala je beta-
blokatore (21,1%), inhibitore angiotenzin-konvertujućeg enzima (28,1%), acetilsalicilnu
kiselinu/nesteroidne antiinflamatorne lekove (21,1% i 29,8%) čija primena može
precipitirati pogoršanje astme. Obeshrabrujuće je da su 26,3% pacijenata pušači, 35,1% ne
zna koji su okidači za njihovu bolest, a samo 1 pacijent koristi astma akcioni plan. Rezultati
ukazuju na veću zastupljenost terapije koja odgovara težim stadijumima astme, što može
ukazivati na lošiju kontrolu bolesti i lošije ishode. Uočava se potreba za uvođenjem usluga
farmaceutske zdravstvene zaštite i boljom edukacijom pacijenata o astmi., Asthma represents a serious global burden because, despite available therapy, poor
health and socio-economic outcomes are reported. The aim of this paper is to analyse
treatment in patients with asthma and to identify drug-related problems. An observational
study included 57 adult asthma patients of both genders. Data were collected in community
pharmacies during 2016, by filling out questionnaires. Descriptive analysis was performed in
Microsoft® Office Excel 2010. Respondents’ average age was 49.7±17.4, 38.6% were men.
Patients used short-acting (36.8%) and long-acting beta-2 agonists (8.8%), inhaled
corticosteroids (28.1%) and combined preparations (73.7%). More than 50% of patients
used inhaled anticholinergics, while theophylline was used in 31.6%, which is in discordance
with the asthma guidelines, due to poor efficacy and safety profile. Also, this may indicate
that patients do not accept inhalation therapy because of demanding technique or higher
cost. Allergic rhinitis, obesity, hypertension, and gastroesophageal reflux disease were the
most common comorbidities. Potentially inadequate co-therapy included beta-blockers
(21.1%), angiotensin-converting enzyme inhibitors (28.1%), aspirin/nonsteroidal
antiinflamatory drugs (21.1% and 29.8%), which may worsen asthma. It is discouraging that
26.3% of patients were smokers, 35.1% did not know the triggers for asthma, and only 1
patient used the asthma action plan. The results show a higher prevalence of therapy
appropriate for severe asthma stages, which implies poor disease control and poor
outcomes. There is a need for the implementation of pharmaceutical care services and better
education of patients with asthma.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Pregled terapije i terapijskih problema kod pacijenata sa astmom u primarnoj zdravstvenoj zaštiti, Review of therapy and therapeutic problems in patients with asthma in primary health care",
volume = "72",
number = "4-suplement",
pages = "S280-S281",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4390"
}

Lazarević, K., Kovačević, M., Ćulafić, M., Jovanović, M., Roganović, M., Vezmar-Kovačević, S., Vučićević, K.,& Miljković, B.. (2022). Pregled terapije i terapijskih problema kod pacijenata sa astmom u primarnoj zdravstvenoj zaštiti. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4-suplement), S280-S281.
https://hdl.handle.net/21.15107/rcub_farfar_4390

Lazarević K, Kovačević M, Ćulafić M, Jovanović M, Roganović M, Vezmar-Kovačević S, Vučićević K, Miljković B. Pregled terapije i terapijskih problema kod pacijenata sa astmom u primarnoj zdravstvenoj zaštiti. in Arhiv za farmaciju. 2022;72(4-suplement):S280-S281.
https://hdl.handle.net/21.15107/rcub_farfar_4390 .

Lazarević, Katarina, Kovačević, Milena, Ćulafić, Milica, Jovanović, Marija, Roganović, Maša, Vezmar-Kovačević, Sandra, Vučićević, Katarina, Miljković, Branislava, "Pregled terapije i terapijskih problema kod pacijenata sa astmom u primarnoj zdravstvenoj zaštiti" in Arhiv za farmaciju, 72, no. 4-suplement (2022):S280-S281,
https://hdl.handle.net/21.15107/rcub_farfar_4390 .

TY  - CONF
AU  - Lazarević, Katarina
AU  - Marković, Aleksandra
AU  - Vezmar-Kovačević, Sandra
AU  - Jovanović, Marija
AU  - Ćulafić, Milica
AU  - Kovačević, Milena
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4389
AB  - Benigna hiperplazija prostate (BHP) predstavlja nekancerozno uvećanje prostate
povezano sa simptomima donjeg urinarnog trakta i spada u najčešća oboljenja starijih
muškaraca. Kako su u ovom dobu uobičajeni komorbiditeti, pre svega kardiovaskularna
(KVS) oboljenja, može se očekivati veliki broj klinički značajnih interakcija lekova. Svrha ove
studije bila je analiza učestalosti i vrste potencijalnih interakcija u terapiji starijih pacijenata
sa BHP i KVS oboljenjem. Sprovedeno retrospektivno istraživanje uključilo je 93 muškaraca
starijih od 65 godina, obolelih od BHP i hipertenzije ili nekog KVS oboljenja. Podaci o
pacijentima su prikupljani iz medicinske dokumentacije. Potencijalne interakcije su
identifikovane i procenjivane korišćenjem Lexicomp® elektronske baze podataka.
Deskriptivna analiza je obavljena u programu Microsoft ® Office Excel 2010. Prosečna starost
ispitanika iznosila je 75,3±6,05. Broj lekova u terapiji bio je u rasponu od 2 do 13. Pet ili više
lekova primenjivalo je 72,04% pacijenata. Detektovano je ukupno 509 interakcija, od kojih
čak 467 spada u klinički značajne (C, D, X). Najveći broj identifikovanih interakcija pripada
klasi C (85,46%), dok je 4,91% iz klase D, a samo 1,38% iz klase X. U okviru klase X, koja
ukazuje da treba izbegavati istovremenu primenu kombinacije lekova, najčešće se javljala
interakcija između dva α-blokatora. Zabeleženo je 412 farmakodinamskih i 47
farmakokinetičkih interakcija. Dvojni mehanizam je detektovan kod 29 interakcija, a 21 se
odvijao nepoznatim mehanizmom. Rezultati studije upućuju da uključivanje farmaceuta u
praćenje pacijenata sa BHP može biti korisno, imajući u vidu značajan broj identifikovanih
klinički značajnih interakcija.
AB  - Benign prostatic hyperplasia (BPH) represents a non-cancerous prostate enlargement
associated with lower urinary tract symptoms and is one of the most common diseases in
older men. As comorbidities, primarily cardiovascular diseases (CVD) are common in this
age group, a great number of clinically significant drug interactions can be expected. The aim
of this research was to estimate the frequency and type of potential interactions in the
treatment of elderly with BPH and CVD. A retrospective study included 93 men aged over 65
with BPH and hypertension or CVD. Patients’ data were collected from medical records.
Potential interactions were identified and assessed using the Lexicomp ® database.
Descriptive analysis was performed in Microsoft® Office Excel 2010. Patients’ average age
was 75.3±6.05. The number of drugs in therapy ranged from 2 to 13. Five or more drugs
were used by 72.04% of the patients. A total of 509 interactions were detected, of which 467
are clinically significant (C, D, X). Most interactions belonged to category C (85.46%), while
4.91% belonged to class D, and only 1.38% to class X. Within class X, which indicates that
concomitant use of drugs should be avoided, the interaction between the two α-blockers was
most frequent. 412 pharmacodynamic and 47 pharmacokinetic interactions were identified.
The dual mechanism was detected in 29 interactions, while for 21 the mechanism was
unknown. The obtained results suggest the involvement of pharmacists in the monitoring of
patients with BPH may be useful, given the great proportion of identified clinically significant
interactions.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Praćenje interakcija lekova kod starijih pacijenata sa benignom hiperplazijom prostate i kardiovaskularnim oboljenjima
T1  - Monitoring of drug interactions in elderly patients with benign prostatic hyperplasia and cardiovascular diseases
VL  - 72
IS  - 4-suplement
SP  - S278
EP  - S279
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4389
ER  - 

@conference{
author = "Lazarević, Katarina and Marković, Aleksandra and Vezmar-Kovačević, Sandra and Jovanović, Marija and Ćulafić, Milica and Kovačević, Milena and Vučićević, Katarina and Miljković, Branislava",
year = "2022",
abstract = "Benigna hiperplazija prostate (BHP) predstavlja nekancerozno uvećanje prostate
povezano sa simptomima donjeg urinarnog trakta i spada u najčešća oboljenja starijih
muškaraca. Kako su u ovom dobu uobičajeni komorbiditeti, pre svega kardiovaskularna
(KVS) oboljenja, može se očekivati veliki broj klinički značajnih interakcija lekova. Svrha ove
studije bila je analiza učestalosti i vrste potencijalnih interakcija u terapiji starijih pacijenata
sa BHP i KVS oboljenjem. Sprovedeno retrospektivno istraživanje uključilo je 93 muškaraca
starijih od 65 godina, obolelih od BHP i hipertenzije ili nekog KVS oboljenja. Podaci o
pacijentima su prikupljani iz medicinske dokumentacije. Potencijalne interakcije su
identifikovane i procenjivane korišćenjem Lexicomp® elektronske baze podataka.
Deskriptivna analiza je obavljena u programu Microsoft ® Office Excel 2010. Prosečna starost
ispitanika iznosila je 75,3±6,05. Broj lekova u terapiji bio je u rasponu od 2 do 13. Pet ili više
lekova primenjivalo je 72,04% pacijenata. Detektovano je ukupno 509 interakcija, od kojih
čak 467 spada u klinički značajne (C, D, X). Najveći broj identifikovanih interakcija pripada
klasi C (85,46%), dok je 4,91% iz klase D, a samo 1,38% iz klase X. U okviru klase X, koja
ukazuje da treba izbegavati istovremenu primenu kombinacije lekova, najčešće se javljala
interakcija između dva α-blokatora. Zabeleženo je 412 farmakodinamskih i 47
farmakokinetičkih interakcija. Dvojni mehanizam je detektovan kod 29 interakcija, a 21 se
odvijao nepoznatim mehanizmom. Rezultati studije upućuju da uključivanje farmaceuta u
praćenje pacijenata sa BHP može biti korisno, imajući u vidu značajan broj identifikovanih
klinički značajnih interakcija., Benign prostatic hyperplasia (BPH) represents a non-cancerous prostate enlargement
associated with lower urinary tract symptoms and is one of the most common diseases in
older men. As comorbidities, primarily cardiovascular diseases (CVD) are common in this
age group, a great number of clinically significant drug interactions can be expected. The aim
of this research was to estimate the frequency and type of potential interactions in the
treatment of elderly with BPH and CVD. A retrospective study included 93 men aged over 65
with BPH and hypertension or CVD. Patients’ data were collected from medical records.
Potential interactions were identified and assessed using the Lexicomp ® database.
Descriptive analysis was performed in Microsoft® Office Excel 2010. Patients’ average age
was 75.3±6.05. The number of drugs in therapy ranged from 2 to 13. Five or more drugs
were used by 72.04% of the patients. A total of 509 interactions were detected, of which 467
are clinically significant (C, D, X). Most interactions belonged to category C (85.46%), while
4.91% belonged to class D, and only 1.38% to class X. Within class X, which indicates that
concomitant use of drugs should be avoided, the interaction between the two α-blockers was
most frequent. 412 pharmacodynamic and 47 pharmacokinetic interactions were identified.
The dual mechanism was detected in 29 interactions, while for 21 the mechanism was
unknown. The obtained results suggest the involvement of pharmacists in the monitoring of
patients with BPH may be useful, given the great proportion of identified clinically significant
interactions.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Praćenje interakcija lekova kod starijih pacijenata sa benignom hiperplazijom prostate i kardiovaskularnim oboljenjima, Monitoring of drug interactions in elderly patients with benign prostatic hyperplasia and cardiovascular diseases",
volume = "72",
number = "4-suplement",
pages = "S278-S279",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4389"
}

Lazarević, K., Marković, A., Vezmar-Kovačević, S., Jovanović, M., Ćulafić, M., Kovačević, M., Vučićević, K.,& Miljković, B.. (2022). Praćenje interakcija lekova kod starijih pacijenata sa benignom hiperplazijom prostate i kardiovaskularnim oboljenjima. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4-suplement), S278-S279.
https://hdl.handle.net/21.15107/rcub_farfar_4389

Lazarević K, Marković A, Vezmar-Kovačević S, Jovanović M, Ćulafić M, Kovačević M, Vučićević K, Miljković B. Praćenje interakcija lekova kod starijih pacijenata sa benignom hiperplazijom prostate i kardiovaskularnim oboljenjima. in Arhiv za farmaciju. 2022;72(4-suplement):S278-S279.
https://hdl.handle.net/21.15107/rcub_farfar_4389 .

Lazarević, Katarina, Marković, Aleksandra, Vezmar-Kovačević, Sandra, Jovanović, Marija, Ćulafić, Milica, Kovačević, Milena, Vučićević, Katarina, Miljković, Branislava, "Praćenje interakcija lekova kod starijih pacijenata sa benignom hiperplazijom prostate i kardiovaskularnim oboljenjima" in Arhiv za farmaciju, 72, no. 4-suplement (2022):S278-S279,
https://hdl.handle.net/21.15107/rcub_farfar_4389 .

TY  - CONF
AU  - Jovanović, Marija
AU  - Roganović, Maša
AU  - Kovačević, Milena
AU  - Ćulafić, Milica
AU  - Vučićević, Katarina
AU  - Vezmar-Kovačević, Sandra
AU  - Milenković, Branislava
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4388
AB  - Lečenje astme i hronične opstruktivne bolesti pluća (HOBP) zahteva optimalnu
upotrebu inhalatora. Farmaceuti imaju značajnu ulogu u edukaciji pacijenata o pravilnoj
upotrebi inhalatora, uključujuć i inhalatore za suvi prašak (eng. Dry Powder Inhalers, DPI). Cilj
studije je bio da se procene i uporede veštine demonstracije farmaceuta za DPI pre i posle
edukacije. U studiju su uključeni samo farmaceuti bez prethodne obuke za pravilnu upotrebu
inhalatora. Skor farmaceuta je procenjen na početku i nakon obuke za pravilnu upotrebu 5
tipova DPI. Učesnici su dobijali 1 poen za svaki od četiri pravilno izvedenih koraka.
Statistička analiza je izvršena korišćenjem SPSS programa (verzija 25). Wilcoxon test je
korišćen za poređenje rezultata pre i posle edukacije. Prosečan skor nakon obuke bio je
3,8±0,57 za sve tipove DPI. Uočena je statistički značajna razlika (p<0,05) u postignutim
skorovama pre i posle obuke farmaceuta uzimajući u obzir 594 poređenja. U 575 slučajeva
skor je bio viši nakon obuke, u samo 2 slučaja skor je bio niži, dok je u 17 slučajeva bio
izjednačen. Ukupna stopa greške za prvi korak (priprema uređaja) bila je 2,86%, za drugi
korak (izdisaj) 4,71%, za treć i korak (udisaj) 6,73% i za poslednji korak (zadržavanje daha)
5,56%. Rezultati ukazuju da je obuka unapredila veštine farmaceuta u vezi sa tehnikom
primene DPI. To može doprineti boljoj kontroli astme i HOBP, nakon edukacije pacijenata.
Ovo je posebno važno imajući u vidu da su farmaceuti najpristupačniji zdravstveni radnici.
AB  - Treatment of asthma and chronic obstructive pulmonary disease (COPD) requires
optimal use of inhalers. Pharmacists have a significant role in educating patients on the
correct use of inhalers, including dry powder inhalers (DPI). The aim of the study was to
assess and compare pharmacists’ DPI technique demonstration skills before and after the
education. The study included only pharmacists without previous training for correct use of
inhalers. Pharmacists’ score was assessed at baseline and after the training of the correct use
of 5 types of DPI. The participants were given a 1-point score for each of four steps
performed correctly. Statistical analysis was performed using the SPSS program (version
25). Wilcoxon test was used for score comparison before and after education. The mean
score after training was 3.8±0.57 for all types of DPI. There was a statistically significant
difference (p<0.05) in achieved scores before and after pharmacists' training taking into
account 594 comparisons. In 575 cases the score was higher after training, in only 2 cases
the score was lower, while in 17 cases it was even. The total error rate for first step (device
preparation) was 2.86%, for second step (expiration) it was 4.71%, for third step
(inhalation) it was 6.73% and for last step (holding breath) it was 5.56%. The results imply
that training improved pharmacist skills regarding the DPI technique. It may contribute to
better control of asthma and COPD, after education of patients. This is especially important
considering that pharmacist are the most accessible health care professionals.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Procena tehnike inhalacije farmaceuta u primarnoj zdravstvenoj zaštiti ‐ fokus na inhalatore za suvi prašak
T1  - Evaluation of inhalation technique of community pharmacists - focus on dry powder inhalers
VL  - 72
IS  - 4-suplement
SP  - S274
EP  - S275
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4388
ER  - 

@conference{
author = "Jovanović, Marija and Roganović, Maša and Kovačević, Milena and Ćulafić, Milica and Vučićević, Katarina and Vezmar-Kovačević, Sandra and Milenković, Branislava and Miljković, Branislava",
year = "2022",
abstract = "Lečenje astme i hronične opstruktivne bolesti pluća (HOBP) zahteva optimalnu
upotrebu inhalatora. Farmaceuti imaju značajnu ulogu u edukaciji pacijenata o pravilnoj
upotrebi inhalatora, uključujuć i inhalatore za suvi prašak (eng. Dry Powder Inhalers, DPI). Cilj
studije je bio da se procene i uporede veštine demonstracije farmaceuta za DPI pre i posle
edukacije. U studiju su uključeni samo farmaceuti bez prethodne obuke za pravilnu upotrebu
inhalatora. Skor farmaceuta je procenjen na početku i nakon obuke za pravilnu upotrebu 5
tipova DPI. Učesnici su dobijali 1 poen za svaki od četiri pravilno izvedenih koraka.
Statistička analiza je izvršena korišćenjem SPSS programa (verzija 25). Wilcoxon test je
korišćen za poređenje rezultata pre i posle edukacije. Prosečan skor nakon obuke bio je
3,8±0,57 za sve tipove DPI. Uočena je statistički značajna razlika (p<0,05) u postignutim
skorovama pre i posle obuke farmaceuta uzimajući u obzir 594 poređenja. U 575 slučajeva
skor je bio viši nakon obuke, u samo 2 slučaja skor je bio niži, dok je u 17 slučajeva bio
izjednačen. Ukupna stopa greške za prvi korak (priprema uređaja) bila je 2,86%, za drugi
korak (izdisaj) 4,71%, za treć i korak (udisaj) 6,73% i za poslednji korak (zadržavanje daha)
5,56%. Rezultati ukazuju da je obuka unapredila veštine farmaceuta u vezi sa tehnikom
primene DPI. To može doprineti boljoj kontroli astme i HOBP, nakon edukacije pacijenata.
Ovo je posebno važno imajući u vidu da su farmaceuti najpristupačniji zdravstveni radnici., Treatment of asthma and chronic obstructive pulmonary disease (COPD) requires
optimal use of inhalers. Pharmacists have a significant role in educating patients on the
correct use of inhalers, including dry powder inhalers (DPI). The aim of the study was to
assess and compare pharmacists’ DPI technique demonstration skills before and after the
education. The study included only pharmacists without previous training for correct use of
inhalers. Pharmacists’ score was assessed at baseline and after the training of the correct use
of 5 types of DPI. The participants were given a 1-point score for each of four steps
performed correctly. Statistical analysis was performed using the SPSS program (version
25). Wilcoxon test was used for score comparison before and after education. The mean
score after training was 3.8±0.57 for all types of DPI. There was a statistically significant
difference (p<0.05) in achieved scores before and after pharmacists' training taking into
account 594 comparisons. In 575 cases the score was higher after training, in only 2 cases
the score was lower, while in 17 cases it was even. The total error rate for first step (device
preparation) was 2.86%, for second step (expiration) it was 4.71%, for third step
(inhalation) it was 6.73% and for last step (holding breath) it was 5.56%. The results imply
that training improved pharmacist skills regarding the DPI technique. It may contribute to
better control of asthma and COPD, after education of patients. This is especially important
considering that pharmacist are the most accessible health care professionals.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Procena tehnike inhalacije farmaceuta u primarnoj zdravstvenoj zaštiti ‐ fokus na inhalatore za suvi prašak, Evaluation of inhalation technique of community pharmacists - focus on dry powder inhalers",
volume = "72",
number = "4-suplement",
pages = "S274-S275",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4388"
}

Jovanović, M., Roganović, M., Kovačević, M., Ćulafić, M., Vučićević, K., Vezmar-Kovačević, S., Milenković, B.,& Miljković, B.. (2022). Procena tehnike inhalacije farmaceuta u primarnoj zdravstvenoj zaštiti ‐ fokus na inhalatore za suvi prašak. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4-suplement), S274-S275.
https://hdl.handle.net/21.15107/rcub_farfar_4388

Jovanović M, Roganović M, Kovačević M, Ćulafić M, Vučićević K, Vezmar-Kovačević S, Milenković B, Miljković B. Procena tehnike inhalacije farmaceuta u primarnoj zdravstvenoj zaštiti ‐ fokus na inhalatore za suvi prašak. in Arhiv za farmaciju. 2022;72(4-suplement):S274-S275.
https://hdl.handle.net/21.15107/rcub_farfar_4388 .

Jovanović, Marija, Roganović, Maša, Kovačević, Milena, Ćulafić, Milica, Vučićević, Katarina, Vezmar-Kovačević, Sandra, Milenković, Branislava, Miljković, Branislava, "Procena tehnike inhalacije farmaceuta u primarnoj zdravstvenoj zaštiti ‐ fokus na inhalatore za suvi prašak" in Arhiv za farmaciju, 72, no. 4-suplement (2022):S274-S275,
https://hdl.handle.net/21.15107/rcub_farfar_4388 .

TY  - CONF
AU  - Homšek, Ana
AU  - Jovanović, Marija
AU  - Roganović, Maša
AU  - Kovačević, Milena
AU  - Ćulafić, Milica
AU  - Vezmar-Kovačević, Sandra
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4387
AB  - Kako glavobolje predstavljaju jedno od najčešćih onesposobljavajućih stanja u svetu, 1
a mogu se lečiti lekovima koji se izdaju bez recepta, uloga farmaceuta u zbrinjavanju ovih
pacijenata prepoznata je kao veoma značajna. Cilj istraživanja bio je da se ispitaju percepcije
farmaceuta u primarnoj zdravstvenoj zaštiti o pružanju usluge pacijentima, kao i o
sprovedenoj edukaciji specijalizovanoj ka glavoboljama. Podaci su prikupljani putem ankete,
prilagođene prema prethodnom radu2 i obrađeni u programima SPSS i Microsoft Excel.
Popunjavanju ankete pristupilo je 43 farmaceuta iz primarne zdravstvene zaštite (90,7%
žene, raspon godina 27-64). Provera pouzdanosti ankete potvrđena je upotrebom Cronbach-
ovog testa (αB = 0,727; αC = 0,880). Najveći broj anketiranih farmaceuta smatra da pažljivo
sluša pacijente sa glavoboljom (65% uvek, 27,9% često), interakcije uvek proverava čak
44,7%, dok o pravilnoj primeni leka njih 86,04% uvek posavetuje pacijenta. Međutim,
34,88% prijavljuje da nikada ne kontaktira lekare ukoliko je lek skup, ne refundira se ili
izaziva neželjenu reakciju koja ograničava primenu, a 32,55% samo ponekad to učini. Većina
farmaceuta smatra da je edukacija korisna za bolje razumevanje pacijenata i savetovanje o
glavoboljama (97,67-100%), dok nešto manji procenat (93,02%) smatra da je edukacija
korisna da lakše prepoznaju pacijenta sa migrenom i upute ga lekaru. Percepcija većine
farmaceuta je da savetuje pacijente o terapiji glavobolje i bez prethodne edukacije, ali da bi
uz edukaciju usluga koju pružaju bila kompletnija. Rezultati studije upućuju da buduće
edukacije treba fokusirati na unapređenje komunikacije sa lekarima.
AB  - Since headaches represent one of the most common disabling conditions in the world1
and can be treated with over-the-counter drugs, the role of pharmacists in caring for these
patients has been recognized as very important. The research aim was to review primary
health care pharmacists’ perception regarding patient service they provide and the
conducted education devoted to headaches. Data were collected through a survey adapted
from the published article 2 and analysed in SPSS and Microsoft Excel. The survey was
completed by 43 primary health care pharmacists (90.7% women, age 27-64). The survey
reliability was verified using the Cronbach’s test (αB = 0.727; αC = 0.880). Most of the
surveyed pharmacists believe that they listen carefully to patients with headaches (65%
always, 27.9% often), 44.7% always check interactions, while 86.04% always advise the
patient on proper drug administration. However, 34.88% report that they never contact
doctors if the drug is expensive, not reimbursable or causes an adverse reaction that limits
its use, and 32.55% only sometimes do so. Most pharmacists believe education was useful to
better understand patients and counsel them about headaches (97.67-100%), while a
slightly smaller percentage (93.02%) thinks it helped them learn to identify a migraine
patient and refer him to a doctor. The perception of most pharmacists is that they advise
patients on headache treatment even without prior education, but after it, the service would
be more complete. The study results indicate that future education should focus on
improving communication with doctors.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Percepcija farmaceuta o pružanju usluge pacijentima sa glavoboljom u primarnoj zdravstvenoj zaštiti
T1  - Pharmacists’ perception about providing services to patients with headaches in primary care
VL  - 72
IS  - 4 suplement
SP  - S264
EP  - S265
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4387
ER  - 

@conference{
author = "Homšek, Ana and Jovanović, Marija and Roganović, Maša and Kovačević, Milena and Ćulafić, Milica and Vezmar-Kovačević, Sandra and Vučićević, Katarina and Miljković, Branislava",
year = "2022",
abstract = "Kako glavobolje predstavljaju jedno od najčešćih onesposobljavajućih stanja u svetu, 1
a mogu se lečiti lekovima koji se izdaju bez recepta, uloga farmaceuta u zbrinjavanju ovih
pacijenata prepoznata je kao veoma značajna. Cilj istraživanja bio je da se ispitaju percepcije
farmaceuta u primarnoj zdravstvenoj zaštiti o pružanju usluge pacijentima, kao i o
sprovedenoj edukaciji specijalizovanoj ka glavoboljama. Podaci su prikupljani putem ankete,
prilagođene prema prethodnom radu2 i obrađeni u programima SPSS i Microsoft Excel.
Popunjavanju ankete pristupilo je 43 farmaceuta iz primarne zdravstvene zaštite (90,7%
žene, raspon godina 27-64). Provera pouzdanosti ankete potvrđena je upotrebom Cronbach-
ovog testa (αB = 0,727; αC = 0,880). Najveći broj anketiranih farmaceuta smatra da pažljivo
sluša pacijente sa glavoboljom (65% uvek, 27,9% često), interakcije uvek proverava čak
44,7%, dok o pravilnoj primeni leka njih 86,04% uvek posavetuje pacijenta. Međutim,
34,88% prijavljuje da nikada ne kontaktira lekare ukoliko je lek skup, ne refundira se ili
izaziva neželjenu reakciju koja ograničava primenu, a 32,55% samo ponekad to učini. Većina
farmaceuta smatra da je edukacija korisna za bolje razumevanje pacijenata i savetovanje o
glavoboljama (97,67-100%), dok nešto manji procenat (93,02%) smatra da je edukacija
korisna da lakše prepoznaju pacijenta sa migrenom i upute ga lekaru. Percepcija većine
farmaceuta je da savetuje pacijente o terapiji glavobolje i bez prethodne edukacije, ali da bi
uz edukaciju usluga koju pružaju bila kompletnija. Rezultati studije upućuju da buduće
edukacije treba fokusirati na unapređenje komunikacije sa lekarima., Since headaches represent one of the most common disabling conditions in the world1
and can be treated with over-the-counter drugs, the role of pharmacists in caring for these
patients has been recognized as very important. The research aim was to review primary
health care pharmacists’ perception regarding patient service they provide and the
conducted education devoted to headaches. Data were collected through a survey adapted
from the published article 2 and analysed in SPSS and Microsoft Excel. The survey was
completed by 43 primary health care pharmacists (90.7% women, age 27-64). The survey
reliability was verified using the Cronbach’s test (αB = 0.727; αC = 0.880). Most of the
surveyed pharmacists believe that they listen carefully to patients with headaches (65%
always, 27.9% often), 44.7% always check interactions, while 86.04% always advise the
patient on proper drug administration. However, 34.88% report that they never contact
doctors if the drug is expensive, not reimbursable or causes an adverse reaction that limits
its use, and 32.55% only sometimes do so. Most pharmacists believe education was useful to
better understand patients and counsel them about headaches (97.67-100%), while a
slightly smaller percentage (93.02%) thinks it helped them learn to identify a migraine
patient and refer him to a doctor. The perception of most pharmacists is that they advise
patients on headache treatment even without prior education, but after it, the service would
be more complete. The study results indicate that future education should focus on
improving communication with doctors.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Percepcija farmaceuta o pružanju usluge pacijentima sa glavoboljom u primarnoj zdravstvenoj zaštiti, Pharmacists’ perception about providing services to patients with headaches in primary care",
volume = "72",
number = "4 suplement",
pages = "S264-S265",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4387"
}

Homšek, A., Jovanović, M., Roganović, M., Kovačević, M., Ćulafić, M., Vezmar-Kovačević, S., Vučićević, K.,& Miljković, B.. (2022). Percepcija farmaceuta o pružanju usluge pacijentima sa glavoboljom u primarnoj zdravstvenoj zaštiti. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S264-S265.
https://hdl.handle.net/21.15107/rcub_farfar_4387

Homšek A, Jovanović M, Roganović M, Kovačević M, Ćulafić M, Vezmar-Kovačević S, Vučićević K, Miljković B. Percepcija farmaceuta o pružanju usluge pacijentima sa glavoboljom u primarnoj zdravstvenoj zaštiti. in Arhiv za farmaciju. 2022;72(4 suplement):S264-S265.
https://hdl.handle.net/21.15107/rcub_farfar_4387 .

Homšek, Ana, Jovanović, Marija, Roganović, Maša, Kovačević, Milena, Ćulafić, Milica, Vezmar-Kovačević, Sandra, Vučićević, Katarina, Miljković, Branislava, "Percepcija farmaceuta o pružanju usluge pacijentima sa glavoboljom u primarnoj zdravstvenoj zaštiti" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S264-S265,
https://hdl.handle.net/21.15107/rcub_farfar_4387 .

TY  - CONF
AU  - Kovačević, Milena
AU  - Ćulafić, Milica
AU  - Roganović, Maša
AU  - Jovanović, Marija
AU  - Vučićević, Katarina
AU  - Vezmar-Kovačević, Sandra
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4396
AB  - Uverenja pacijenata mogu značajno uticati na stepen adherence i ishode terapije
hroničnih oboljenja. Cilj istraživanja bila je procena negativnih stavova (zabrinutosti)
odraslih pacijenata prema primeni terapije u lečenju astme i hronične opstruktivne bolesti
pluća (HOBP). Upitnik je obuhvatio demografske, podatke o terapiji, podatke o kontroli
bolesti (modified Medical Research Council–mMRC u HOBP, i Asthma Control Test–ACT u
astmi), i stavovima u pogledu zabrinutosti (Beliefs about Medicines Questionnaire-BMQ).
Korišćena je petostepena Likertova skala (1-uopšte se ne slažem, do 5–u potpunosti se
slažem). Analiza je izvršena primenom SPSS softvera (ver. 27). Istraživanjem je obuhvaćeno
145 pacijenata, 80 sa HOBP (55,2%) i 65 sa astmom (44,8%). Adekvatna kontrola bolesti
zabeležena je kod 42% (45% mMRC<2, 38,5% ACT≥20). Prosečna vrednost skora
zabrinutosti iznosila je 14,7±4,2 (opseg 6-25). Vrednost se nije statistički značajno
razlikovala između pacijenata sa astmom i HOBP, niti u zavisnosti od dužine trajanja bolesti.
Zabrinutost zbog primene lekova izrazilo je 55,9% pacijenata, dugoročnih posledica 44,1%,
razvoja zavisnosti 32,4%, nepoznavanja lekova 29,7% i uticaja na svakodnevni život 24,1%.
Literaturni podaci ukazuju na jaku povezanost negativnih stavova prema lekovima sa nižim
stepenom adherence, što nije bila tema našeg istraživanja, ali se može pretpostaviti da ti
rezultati doprinose lošoj kontroli bolesti u ispitivanoj grupi (<50%). Savetovanje pacijenata
u javnim apotekama o značaju redovne primene i odnosu korist/rizik od primene lekova u
lečenju astme i HOBP može biti značajna intervencija ka unapređenju stavova i ishoda
terapije.
AB  - Patients’ beliefs can significantly impact the adherence and outcomes of chronic
disease therapy. The aim of the study was to assess the negative attitudes (concerns) of adult
patients towards the use of medications for asthma and chronic obstructive pulmonary
disease (COPD). The questionnaire included demographics, data on therapy, disease control
(modified Medical Research Council-mMRC for COPD, and Asthma Control Test-ACT), and
concerns (Beliefs about Medicines Questionnaire-BMQ). A five-point Likert scale was used
(1-strongly disagree, to 5-strongly agree). Analysis was performed using SPSS software (ver.
27). The study included 145 patients, 80 COPD (55.2%) and 65 asthma (44.8%). Adequate
disease control was observed in 42% (45% mMRC <2, 38.5% ACT≥20). The mean concern
score was 14.7±4.2 (range 6–25). The score did not differ significantly between the patients
with asthma and COPD, nor depending on the disease duration. Concerns about the regular
use of medications were expressed by 55.9%, long-term consequences 44.1%, development
of addiction 32.4%, lack of knowledge 29.7% and the impact on everyday life 24.1%.
Literature data indicate a strong correlation between negative attitudes towards
medications with a lower level of adherence. It can be assumed that these results contribute
to poor disease control observed in our study (<50%). Patients’ counseling on the
importance of regular use and the benefit/risk ratio of asthma and COPD medications can be
a meaningful intervention in improving attitudes and therapy outcomes.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Zabrinutost u vezi sa primenom lekova kod pacijenata sa hroničnim respiratornim oboljenjima
T1  - Concerns about medications in patients with chronic respiratory disease
VL  - 72
IS  - 4 Suplement
SP  - S256
EP  - S257
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4396
ER  - 

@conference{
author = "Kovačević, Milena and Ćulafić, Milica and Roganović, Maša and Jovanović, Marija and Vučićević, Katarina and Vezmar-Kovačević, Sandra and Miljković, Branislava",
year = "2022",
abstract = "Uverenja pacijenata mogu značajno uticati na stepen adherence i ishode terapije
hroničnih oboljenja. Cilj istraživanja bila je procena negativnih stavova (zabrinutosti)
odraslih pacijenata prema primeni terapije u lečenju astme i hronične opstruktivne bolesti
pluća (HOBP). Upitnik je obuhvatio demografske, podatke o terapiji, podatke o kontroli
bolesti (modified Medical Research Council–mMRC u HOBP, i Asthma Control Test–ACT u
astmi), i stavovima u pogledu zabrinutosti (Beliefs about Medicines Questionnaire-BMQ).
Korišćena je petostepena Likertova skala (1-uopšte se ne slažem, do 5–u potpunosti se
slažem). Analiza je izvršena primenom SPSS softvera (ver. 27). Istraživanjem je obuhvaćeno
145 pacijenata, 80 sa HOBP (55,2%) i 65 sa astmom (44,8%). Adekvatna kontrola bolesti
zabeležena je kod 42% (45% mMRC<2, 38,5% ACT≥20). Prosečna vrednost skora
zabrinutosti iznosila je 14,7±4,2 (opseg 6-25). Vrednost se nije statistički značajno
razlikovala između pacijenata sa astmom i HOBP, niti u zavisnosti od dužine trajanja bolesti.
Zabrinutost zbog primene lekova izrazilo je 55,9% pacijenata, dugoročnih posledica 44,1%,
razvoja zavisnosti 32,4%, nepoznavanja lekova 29,7% i uticaja na svakodnevni život 24,1%.
Literaturni podaci ukazuju na jaku povezanost negativnih stavova prema lekovima sa nižim
stepenom adherence, što nije bila tema našeg istraživanja, ali se može pretpostaviti da ti
rezultati doprinose lošoj kontroli bolesti u ispitivanoj grupi (<50%). Savetovanje pacijenata
u javnim apotekama o značaju redovne primene i odnosu korist/rizik od primene lekova u
lečenju astme i HOBP može biti značajna intervencija ka unapređenju stavova i ishoda
terapije., Patients’ beliefs can significantly impact the adherence and outcomes of chronic
disease therapy. The aim of the study was to assess the negative attitudes (concerns) of adult
patients towards the use of medications for asthma and chronic obstructive pulmonary
disease (COPD). The questionnaire included demographics, data on therapy, disease control
(modified Medical Research Council-mMRC for COPD, and Asthma Control Test-ACT), and
concerns (Beliefs about Medicines Questionnaire-BMQ). A five-point Likert scale was used
(1-strongly disagree, to 5-strongly agree). Analysis was performed using SPSS software (ver.
27). The study included 145 patients, 80 COPD (55.2%) and 65 asthma (44.8%). Adequate
disease control was observed in 42% (45% mMRC <2, 38.5% ACT≥20). The mean concern
score was 14.7±4.2 (range 6–25). The score did not differ significantly between the patients
with asthma and COPD, nor depending on the disease duration. Concerns about the regular
use of medications were expressed by 55.9%, long-term consequences 44.1%, development
of addiction 32.4%, lack of knowledge 29.7% and the impact on everyday life 24.1%.
Literature data indicate a strong correlation between negative attitudes towards
medications with a lower level of adherence. It can be assumed that these results contribute
to poor disease control observed in our study (<50%). Patients’ counseling on the
importance of regular use and the benefit/risk ratio of asthma and COPD medications can be
a meaningful intervention in improving attitudes and therapy outcomes.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Zabrinutost u vezi sa primenom lekova kod pacijenata sa hroničnim respiratornim oboljenjima, Concerns about medications in patients with chronic respiratory disease",
volume = "72",
number = "4 Suplement",
pages = "S256-S257",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4396"
}

Kovačević, M., Ćulafić, M., Roganović, M., Jovanović, M., Vučićević, K., Vezmar-Kovačević, S.,& Miljković, B.. (2022). Zabrinutost u vezi sa primenom lekova kod pacijenata sa hroničnim respiratornim oboljenjima. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 Suplement), S256-S257.
https://hdl.handle.net/21.15107/rcub_farfar_4396

Kovačević M, Ćulafić M, Roganović M, Jovanović M, Vučićević K, Vezmar-Kovačević S, Miljković B. Zabrinutost u vezi sa primenom lekova kod pacijenata sa hroničnim respiratornim oboljenjima. in Arhiv za farmaciju. 2022;72(4 Suplement):S256-S257.
https://hdl.handle.net/21.15107/rcub_farfar_4396 .

Kovačević, Milena, Ćulafić, Milica, Roganović, Maša, Jovanović, Marija, Vučićević, Katarina, Vezmar-Kovačević, Sandra, Miljković, Branislava, "Zabrinutost u vezi sa primenom lekova kod pacijenata sa hroničnim respiratornim oboljenjima" in Arhiv za farmaciju, 72, no. 4 Suplement (2022):S256-S257,
https://hdl.handle.net/21.15107/rcub_farfar_4396 .