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  - Milosavljević, Miloš
AU  - Okanović, Milan
AU  - Cicvarić Kostić, Slavica
AU  - Jovanović, Marija
AU  - Radonić, Milenko
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4473
AB  - Banknotes and coins are some of the most frequently traded items in the world. Their current use, however, is unsustainable, and many countries are trying to digitalize their payment systems. The recent pandemic has accelerated this transition. Building on the Theory of Unintended Consequences, the aim of this article is to examine the influence of some pandemic-specific factors (in specific, hand sanitization, conspiracy theory mentality, and financial acumen) on the current and prospective use of e-payment. A particular aim of the study is to analyze these relationships in Serbia (as an example of a cash-centric society). The study is based on primary data gathered via a questionnaire. The questionnaire was designed for the purpose of this study. In total, the study examined N = 474 examinees. The results of this study confirm that the pandemic-induced variables are statistically significant predictors of e-payment use. In particular, hand sanitization, conspiracy mentality (reversely), and financial acumen positively affect current and prospective e-payment use.
PB  - MDPI
T2  - Sustainability
T1  - COVID-19 and Behavioral Factors of e-Payment Use: Evidence from Serbia
VL  - 15
IS  - 4
DO  - 10.3390/su15043188
ER  - 

@article{
author = "Milosavljević, Miloš and Okanović, Milan and Cicvarić Kostić, Slavica and Jovanović, Marija and Radonić, Milenko",
year = "2023",
abstract = "Banknotes and coins are some of the most frequently traded items in the world. Their current use, however, is unsustainable, and many countries are trying to digitalize their payment systems. The recent pandemic has accelerated this transition. Building on the Theory of Unintended Consequences, the aim of this article is to examine the influence of some pandemic-specific factors (in specific, hand sanitization, conspiracy theory mentality, and financial acumen) on the current and prospective use of e-payment. A particular aim of the study is to analyze these relationships in Serbia (as an example of a cash-centric society). The study is based on primary data gathered via a questionnaire. The questionnaire was designed for the purpose of this study. In total, the study examined N = 474 examinees. The results of this study confirm that the pandemic-induced variables are statistically significant predictors of e-payment use. In particular, hand sanitization, conspiracy mentality (reversely), and financial acumen positively affect current and prospective e-payment use.",
publisher = "MDPI",
journal = "Sustainability",
title = "COVID-19 and Behavioral Factors of e-Payment Use: Evidence from Serbia",
volume = "15",
number = "4",
doi = "10.3390/su15043188"
}

Milosavljević, M., Okanović, M., Cicvarić Kostić, S., Jovanović, M.,& Radonić, M.. (2023). COVID-19 and Behavioral Factors of e-Payment Use: Evidence from Serbia. in Sustainability
MDPI., 15(4).
https://doi.org/10.3390/su15043188

Milosavljević M, Okanović M, Cicvarić Kostić S, Jovanović M, Radonić M. COVID-19 and Behavioral Factors of e-Payment Use: Evidence from Serbia. in Sustainability. 2023;15(4).
doi:10.3390/su15043188 .

Milosavljević, Miloš, Okanović, Milan, Cicvarić Kostić, Slavica, Jovanović, Marija, Radonić, Milenko, "COVID-19 and Behavioral Factors of e-Payment Use: Evidence from Serbia" in Sustainability, 15, no. 4 (2023),
https://doi.org/10.3390/su15043188 . .

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  - 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  - 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 .

TY  - CONF
AU  - Kovačević, Milena
AU  - Jovanović, Marija
AU  - Ćulafić, Milica
AU  - Roganović, Maša
AU  - Vučićević, Katarina
AU  - Vezmar-Kovačević, Sandra
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4386
AB  - Primena benzodiazepina kod starijih pacijenata povezana je sa brojnim neželjenim
ishodima, poput povećanog rizika od pada, fraktura, troškova u zdravstvenom sistemu, pa
čak i smrtnih ishoda. Cilj rada bio je određivanje učestalosti primene benzodiazepina kod
pacijenata starosti ≥65 godina, i procena povezanosti njihove primene sa karakteristikama
pacijenata. Podaci su prikupljeni prospektivno u javnim apotekama primenom upitnika koji
su obuhvatili demografske, kliničke i karakteristike terapije pacijenta. Obrada rezultata
izvršena je primenom softvera SPSS (ver. 25). U istraživanju je učestvovalo 287 pacijenata,
prosečne starosti 72,2±5,8 godina (ukupan opseg 65-91). Prosečan broj lekova po pacijentu
iznosio je 7,6±2,2 (4-18), dok je prosečan broj indikacija iznosio 4,5±1,7 (1-11). Ukupna
zastupljenost benzodiazepina iznosila je 28,9%, od čega su dugodelujući bili primenjivani
kod 24.0%, a kratkodelujući kod 5,2% pacijenata. Najčešće primenjivan lek iz ove grupe bio
je bromazepam (17,1%), potom diazepam (7.0%), lorazepam (3,8%) i alprazolam (1,4%). U
grupi pacijenata starosti 65-69 godina prevalenca primene benzodiazepina iznosila je 29,3%,
70-74 godina 33,7%, 75-80 godina 23,3% i kod starijih od 80 godina 24.0%. Primena
benzodiazepina bila je statistički značajno češća kod pacijenata sa dijagnozom anksioznosti,
drugog mentalnog oboljenja, ali i primenom bisfosfonata, analgetika ili biljnog leka ekstrakta
lista Ginko biloba (p<0,05). Određena je visoka učestalost primene benzodiazepina kod
starijih pacijenata. Farmaceuti u javnim apotekama mogu imati značajnu ulogu u proceni i
minimizaciji rizika od neželjenog događaja, koji uključuju savetovanje pacijenata o prevenciji
padova, ali i mogućnostima postepene obustave ovih lekova kada ne postoji ubedljiva
indikacija za njihovu dugotrajnu primenu.
AB  - The use of benzodiazepines in elderly patients is associated with the numerous adverse
outcomes, such as an increased risk of falls, fractures, health care costs, and even mortality.
The aim was to investigate the frequency of benzodiazepine use in patients aged ≥65 years,
and to explore the association of their use with patient characteristics. Demographic, clinical,
and therapy characteristics were collected prospectively in the community pharmacies. Data
analysis was performed using SPSS software (ver. 25). The study included 287 patients, with
a mean age of 72.2±5.8 years (total range 65-91), the average number of drugs 7.6±2.2 (4-
18), and the average number of indications 4.5±1.7 (1-11). The total prevalence of
benzodiazepine use was 28.9%, long-acting 24.0% and short-acting 5.2%. The most
commonly used was bromazepam (17.1%), followed by diazepam (7.0%), lorazepam (3.8%)
and alprazolam (1.4%). In the patients aged 65-69 years, the prevalence of benzodiazepine
use was 29.3%, 70-74 years 33.7%, 75-80 years 23.3% and in ≥80 years 24.0%. The use of
benzodiazepines was statistically significantly more common in patients diagnosed with
anxiety, other mental illness, but also with the comedication with bisphosphonates,
analgesics or herbal medicine Ginkgo biloba leaf extract (p<0.05). A high frequency of
benzodiazepine use was determined in elderly patients. Community pharmacists can play a
significant role in assessing and minimizing the risk of adverse events. Interventions may
include counseling on the prevention of falls, but also the possibility of drug discontinuation
when there is no convincing indication for their long-term use.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Učestalost primene benzodiazepina kod starijih pacijenata u primarnoj zdravstvenoj zaštiti
T1  - Frequency of benzodiazepine use in elderly primary care patients
VL  - 72
IS  - 4 suplement
SP  - S258
EP  - S259
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4386
ER  - 

@conference{
author = "Kovačević, Milena and Jovanović, Marija and Ćulafić, Milica and Roganović, Maša and Vučićević, Katarina and Vezmar-Kovačević, Sandra and Miljković, Branislava",
year = "2022",
abstract = "Primena benzodiazepina kod starijih pacijenata povezana je sa brojnim neželjenim
ishodima, poput povećanog rizika od pada, fraktura, troškova u zdravstvenom sistemu, pa
čak i smrtnih ishoda. Cilj rada bio je određivanje učestalosti primene benzodiazepina kod
pacijenata starosti ≥65 godina, i procena povezanosti njihove primene sa karakteristikama
pacijenata. Podaci su prikupljeni prospektivno u javnim apotekama primenom upitnika koji
su obuhvatili demografske, kliničke i karakteristike terapije pacijenta. Obrada rezultata
izvršena je primenom softvera SPSS (ver. 25). U istraživanju je učestvovalo 287 pacijenata,
prosečne starosti 72,2±5,8 godina (ukupan opseg 65-91). Prosečan broj lekova po pacijentu
iznosio je 7,6±2,2 (4-18), dok je prosečan broj indikacija iznosio 4,5±1,7 (1-11). Ukupna
zastupljenost benzodiazepina iznosila je 28,9%, od čega su dugodelujući bili primenjivani
kod 24.0%, a kratkodelujući kod 5,2% pacijenata. Najčešće primenjivan lek iz ove grupe bio
je bromazepam (17,1%), potom diazepam (7.0%), lorazepam (3,8%) i alprazolam (1,4%). U
grupi pacijenata starosti 65-69 godina prevalenca primene benzodiazepina iznosila je 29,3%,
70-74 godina 33,7%, 75-80 godina 23,3% i kod starijih od 80 godina 24.0%. Primena
benzodiazepina bila je statistički značajno češća kod pacijenata sa dijagnozom anksioznosti,
drugog mentalnog oboljenja, ali i primenom bisfosfonata, analgetika ili biljnog leka ekstrakta
lista Ginko biloba (p<0,05). Određena je visoka učestalost primene benzodiazepina kod
starijih pacijenata. Farmaceuti u javnim apotekama mogu imati značajnu ulogu u proceni i
minimizaciji rizika od neželjenog događaja, koji uključuju savetovanje pacijenata o prevenciji
padova, ali i mogućnostima postepene obustave ovih lekova kada ne postoji ubedljiva
indikacija za njihovu dugotrajnu primenu., The use of benzodiazepines in elderly patients is associated with the numerous adverse
outcomes, such as an increased risk of falls, fractures, health care costs, and even mortality.
The aim was to investigate the frequency of benzodiazepine use in patients aged ≥65 years,
and to explore the association of their use with patient characteristics. Demographic, clinical,
and therapy characteristics were collected prospectively in the community pharmacies. Data
analysis was performed using SPSS software (ver. 25). The study included 287 patients, with
a mean age of 72.2±5.8 years (total range 65-91), the average number of drugs 7.6±2.2 (4-
18), and the average number of indications 4.5±1.7 (1-11). The total prevalence of
benzodiazepine use was 28.9%, long-acting 24.0% and short-acting 5.2%. The most
commonly used was bromazepam (17.1%), followed by diazepam (7.0%), lorazepam (3.8%)
and alprazolam (1.4%). In the patients aged 65-69 years, the prevalence of benzodiazepine
use was 29.3%, 70-74 years 33.7%, 75-80 years 23.3% and in ≥80 years 24.0%. The use of
benzodiazepines was statistically significantly more common in patients diagnosed with
anxiety, other mental illness, but also with the comedication with bisphosphonates,
analgesics or herbal medicine Ginkgo biloba leaf extract (p<0.05). A high frequency of
benzodiazepine use was determined in elderly patients. Community pharmacists can play a
significant role in assessing and minimizing the risk of adverse events. Interventions may
include counseling on the prevention of falls, but also the possibility of drug discontinuation
when there is no convincing indication for their long-term use.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Učestalost primene benzodiazepina kod starijih pacijenata u primarnoj zdravstvenoj zaštiti, Frequency of benzodiazepine use in elderly primary care patients",
volume = "72",
number = "4 suplement",
pages = "S258-S259",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4386"
}

Kovačević, M., Jovanović, M., Ćulafić, M., Roganović, M., Vučićević, K., Vezmar-Kovačević, S.,& Miljković, B.. (2022). Učestalost primene benzodiazepina kod starijih pacijenata u primarnoj zdravstvenoj zaštiti. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S258-S259.
https://hdl.handle.net/21.15107/rcub_farfar_4386

Kovačević M, Jovanović M, Ćulafić M, Roganović M, Vučićević K, Vezmar-Kovačević S, Miljković B. Učestalost primene benzodiazepina kod starijih pacijenata u primarnoj zdravstvenoj zaštiti. in Arhiv za farmaciju. 2022;72(4 suplement):S258-S259.
https://hdl.handle.net/21.15107/rcub_farfar_4386 .

Kovačević, Milena, Jovanović, Marija, Ćulafić, Milica, Roganović, Maša, Vučićević, Katarina, Vezmar-Kovačević, Sandra, Miljković, Branislava, "Učestalost primene benzodiazepina kod starijih pacijenata u primarnoj zdravstvenoj zaštiti" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S258-S259,
https://hdl.handle.net/21.15107/rcub_farfar_4386 .

TY  - JOUR
AU  - Ćulafić, Milica
AU  - Kovačević, Milena
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/123456789/4383
AB  - COPD is a chronic condition requiring care from a multidisciplinary team in which pharma-
cists play an important role. We aimed to evaluate the impact of structured pharmacist-patient counsel-
ing on patients’ knowledge, and attitudes about medicines and the impact of COPD on patients’ health
status. A prospective study was conducted in ten community pharmacies. Patients were counseled using
a detailed approach after completing validated questionnaires. The patients returned to a pharmacy for
a follow-up after three months. Four validated questionnaires have been used to assess different aspects
of patient’s knowledge about the disease, their attitudes about medicines, and the impact of the disease on
patients’ health status: COPD Assessment Test (CAT), Modified Medical Research Council Dyspnea Scale
(mMRC), Bristol COPD Knowledge Questionnaire (BCKQ), and The Beliefs about Medicines Question-
naire (BMQ). Pharmacists recruited 83 COPD patients, from which 73 patients attended a follow-up visit.
Before pharmacist intervention, the CAT median score was 20. After counseling, the CAT score decreased
to 18 (p < 0.05). The highest improvement in patient knowledge was observed for inhaled bronchodila-
tors (28.2%), vaccination (25.8%), oral steroids (24.4%), and smoking (24.2%). The median score for
necessity increased, whereas the harm and concern median scores considerably decreased (p < 0.05) after
counseling. The results showed significant improvements in all aspects covered throughout pharmacist-
patient counseling. Based on our results, the proactive role of the pharmacist in the care of COPD patients
may be beneficial to patients, physicians, and healthcare by improving care, and alleviating the strain on
overloaded doctors by containing the costs.
PB  - Polish Pharmaceutical Society
T2  - Acta Poloniae Pharmaceutica - Drug Research
T1  - Community pharmacist-driven interventions in COPD: improving knowledge, attitude and health status
VL  - 79
IS  - 5
SP  - 725
EP  - 734
DO  - 10.32383/appdr/155353
ER  - 

@article{
author = "Ćulafić, Milica and Kovačević, Milena and Jovanović, Marija and Roganović, Maša and Vezmar-Kovačević, Sandra and Vučićević, Katarina and Miljković, Branislava",
year = "2022",
abstract = "COPD is a chronic condition requiring care from a multidisciplinary team in which pharma-
cists play an important role. We aimed to evaluate the impact of structured pharmacist-patient counsel-
ing on patients’ knowledge, and attitudes about medicines and the impact of COPD on patients’ health
status. A prospective study was conducted in ten community pharmacies. Patients were counseled using
a detailed approach after completing validated questionnaires. The patients returned to a pharmacy for
a follow-up after three months. Four validated questionnaires have been used to assess different aspects
of patient’s knowledge about the disease, their attitudes about medicines, and the impact of the disease on
patients’ health status: COPD Assessment Test (CAT), Modified Medical Research Council Dyspnea Scale
(mMRC), Bristol COPD Knowledge Questionnaire (BCKQ), and The Beliefs about Medicines Question-
naire (BMQ). Pharmacists recruited 83 COPD patients, from which 73 patients attended a follow-up visit.
Before pharmacist intervention, the CAT median score was 20. After counseling, the CAT score decreased
to 18 (p < 0.05). The highest improvement in patient knowledge was observed for inhaled bronchodila-
tors (28.2%), vaccination (25.8%), oral steroids (24.4%), and smoking (24.2%). The median score for
necessity increased, whereas the harm and concern median scores considerably decreased (p < 0.05) after
counseling. The results showed significant improvements in all aspects covered throughout pharmacist-
patient counseling. Based on our results, the proactive role of the pharmacist in the care of COPD patients
may be beneficial to patients, physicians, and healthcare by improving care, and alleviating the strain on
overloaded doctors by containing the costs.",
publisher = "Polish Pharmaceutical Society",
journal = "Acta Poloniae Pharmaceutica - Drug Research",
title = "Community pharmacist-driven interventions in COPD: improving knowledge, attitude and health status",
volume = "79",
number = "5",
pages = "725-734",
doi = "10.32383/appdr/155353"
}

Ćulafić, M., Kovačević, M., Jovanović, M., Roganović, M., Vezmar-Kovačević, S., Vučićević, K.,& Miljković, B.. (2022). Community pharmacist-driven interventions in COPD: improving knowledge, attitude and health status. in Acta Poloniae Pharmaceutica - Drug Research
Polish Pharmaceutical Society., 79(5), 725-734.
https://doi.org/10.32383/appdr/155353

Ćulafić M, Kovačević M, Jovanović M, Roganović M, Vezmar-Kovačević S, Vučićević K, Miljković B. Community pharmacist-driven interventions in COPD: improving knowledge, attitude and health status. in Acta Poloniae Pharmaceutica - Drug Research. 2022;79(5):725-734.
doi:10.32383/appdr/155353 .

Ćulafić, Milica, Kovačević, Milena, Jovanović, Marija, Roganović, Maša, Vezmar-Kovačević, Sandra, Vučićević, Katarina, Miljković, Branislava, "Community pharmacist-driven interventions in COPD: improving knowledge, attitude and health status" in Acta Poloniae Pharmaceutica - Drug Research, 79, no. 5 (2022):725-734,
https://doi.org/10.32383/appdr/155353 . .

TY  - JOUR
AU  - Homšek, Ana
AU  - Roganović, Maša
AU  - Kovačević, Milena
AU  - Jovanović, Marija
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4376
AB  - Thyroid dysfunction is one of the most prevalent endocrine disorders, especially common
in female patients. If patients are not diagnosed in time or adequately treated, the patients’ quality
of life can be significantly impaired and additional health problems may occur, considering the
key roles of thyroid hormones in the body. Therefore, it is necessary to raise awareness about the
importance of recognition of symptoms that may indicate a potential problem with the thyroid
gland and help to identify possible causes. For patients who are already being treated with
levothyroxine (hypothyroidism), or thiamazole, carbimazole or propylthiouracil
(hyperthyroidism), it is necessary to point out the necessity of proper, regular use of the drugs and
implementation of accompanying nonpharmacological measures, as well as the potential for the
occurrence of adverse reactions and interactions with other drugs or food. A significant role in
the mentioned activities should be played by the pharmacist, as the most accessible member of
the health team, who can, if necessary, refer the patient to a doctor for diagnosis, monitor the
effectiveness and safety of the therapy, and provide appropriate patient counseling.
AB  - Poremećaj funkcije tiroidne žlezde spada u najčešće endokrine poremećaje, posebno u ženskoj populaciji. Ukoliko se poremećaj ne ustanovi na vreme i ne leči adekvatno, kvalitet života pacijenta može biti narušen i može doći do dodatnih zdravstvenih problema, s obzirom na ključne uloge koje tireoidni hormoni imaju u organizmu. Stoga je neophodno podići svest o važnosti prepoznavanja simptoma koji ukazuju na potencijalni problem sa štitnom žlezdom, kao i moguće uzroke. Kod pacijenata koji su na terapiji levotiroksinom (hipotireoidizam) ili tiamazolom, karbimazolom ili propiltiouracilom (hipertireoidizam), potrebno je ukazati na značaj pravilne i redovne upotrebe lekova, uz sprovođenje pratećih nefarmakoloških mera, i ukazati na potencijal za pojavu neželjenih reakcija i interakcija sa drugim lekovima/hranom. Značajnu ulogu u navedenim aktivnostima bi trebalo da ima farmaceut, kao najdostupniji član zdravstvenog tima, koji može uputiti pacijenta lekaru radi postavljanje dijagnoze, pratiti efikasnost i bezbednost terapije, i pružiti pacijentu adekvatno savetovanje.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Role of pharmacists in management of patients with thyroid disorders
T1  - Uloga farmaceuta u zbrinjavanju pacijenta sa poremećajem rada tiroidne žlezde
VL  - 72
IS  - 5
SP  - 486
EP  - 502
DO  - 10.5937/arhfarm72-39948
ER  - 

@article{
author = "Homšek, Ana and Roganović, Maša and Kovačević, Milena and Jovanović, Marija",
year = "2022",
abstract = "Thyroid dysfunction is one of the most prevalent endocrine disorders, especially common
in female patients. If patients are not diagnosed in time or adequately treated, the patients’ quality
of life can be significantly impaired and additional health problems may occur, considering the
key roles of thyroid hormones in the body. Therefore, it is necessary to raise awareness about the
importance of recognition of symptoms that may indicate a potential problem with the thyroid
gland and help to identify possible causes. For patients who are already being treated with
levothyroxine (hypothyroidism), or thiamazole, carbimazole or propylthiouracil
(hyperthyroidism), it is necessary to point out the necessity of proper, regular use of the drugs and
implementation of accompanying nonpharmacological measures, as well as the potential for the
occurrence of adverse reactions and interactions with other drugs or food. A significant role in
the mentioned activities should be played by the pharmacist, as the most accessible member of
the health team, who can, if necessary, refer the patient to a doctor for diagnosis, monitor the
effectiveness and safety of the therapy, and provide appropriate patient counseling., Poremećaj funkcije tiroidne žlezde spada u najčešće endokrine poremećaje, posebno u ženskoj populaciji. Ukoliko se poremećaj ne ustanovi na vreme i ne leči adekvatno, kvalitet života pacijenta može biti narušen i može doći do dodatnih zdravstvenih problema, s obzirom na ključne uloge koje tireoidni hormoni imaju u organizmu. Stoga je neophodno podići svest o važnosti prepoznavanja simptoma koji ukazuju na potencijalni problem sa štitnom žlezdom, kao i moguće uzroke. Kod pacijenata koji su na terapiji levotiroksinom (hipotireoidizam) ili tiamazolom, karbimazolom ili propiltiouracilom (hipertireoidizam), potrebno je ukazati na značaj pravilne i redovne upotrebe lekova, uz sprovođenje pratećih nefarmakoloških mera, i ukazati na potencijal za pojavu neželjenih reakcija i interakcija sa drugim lekovima/hranom. Značajnu ulogu u navedenim aktivnostima bi trebalo da ima farmaceut, kao najdostupniji član zdravstvenog tima, koji može uputiti pacijenta lekaru radi postavljanje dijagnoze, pratiti efikasnost i bezbednost terapije, i pružiti pacijentu adekvatno savetovanje.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Role of pharmacists in management of patients with thyroid disorders, Uloga farmaceuta u zbrinjavanju pacijenta sa poremećajem rada tiroidne žlezde",
volume = "72",
number = "5",
pages = "486-502",
doi = "10.5937/arhfarm72-39948"
}

Homšek, A., Roganović, M., Kovačević, M.,& Jovanović, M.. (2022). Role of pharmacists in management of patients with thyroid disorders. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 72(5), 486-502.
https://doi.org/10.5937/arhfarm72-39948

Homšek A, Roganović M, Kovačević M, Jovanović M. Role of pharmacists in management of patients with thyroid disorders. in Arhiv za farmaciju. 2022;72(5):486-502.
doi:10.5937/arhfarm72-39948 .

Homšek, Ana, Roganović, Maša, Kovačević, Milena, Jovanović, Marija, "Role of pharmacists in management of patients with thyroid disorders" in Arhiv za farmaciju, 72, no. 5 (2022):486-502,
https://doi.org/10.5937/arhfarm72-39948 . .

TY  - CONF
AU  - Jovanović, Marija
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4442
AB  - Psychiatric disorders significantly contribute to the overall burden of diseases in the
world's population. Antipsychotic drug therapy is the main treatment for patients with
schizophrenia or psychosis. These drugs show great variability in pharmacokinetic
characteristics, and consequently in drug level and therapeutic response. Therefore,
Therapeutic Drug Monitoring (TDM) is recommended for many drugs from this group (1).
Sources of variability can be demographic characteristics, pathological or genetic factors.
Moreover, pharmacokinetic, but also pharmacodynamic interactions may significantly
contribute to the variability in drug response. Monitoring of clozapine antipsychotic therapy
and potential interactions will be presented on the adult psychiatric patients. The analysis of
potential drug-drug interactions was performed considering all administered drugs. In
general, pharmacodynamic interactions may cause additive, synergistic, or antagonistic
effects between drugs. In the study population, interactions related to enhanced adverse
effect of clozapine have often been described. Regarding pharmacokinetic interactions, the
most common are those related to the induction or inhibition of cytochrome P450 (CYP 450)
metabolic isoenzymes. Hence, the effect of valproic acid on clozapine metabolism has been
detected in several occasions. Further analysis of TDM data contributes to the understanding
of the effect of this antiepileptic drug on clozapine levels. Monitoring drug variability is the
basis for optimizing the treatment of psychiatric disorders. In collaboration with other
health care professionals, pharmacists have a significant role in dosing optimization,
especially in the prevention and management of drug-drug interactions.
AB  - Psihijatrijska oboljenja u značajnoj meri doprinose ukupnom opterećenju bolesti
svetske populacije. Antipsihotici su osnovni lekovi u terapiji shizofrenije i psihoza. Ovi lekovi
pokazuju veliku varijabilnost u farmakokinetičkim karakteristikama, a samim tim i u
koncentraciji i terapijskom odgovoru. Stoga je terapijsko praćenje lekova (Therapeutic Drug
Monitoring, TDM) preporučeno za mnoge lekove iz ove grupe (1). Izvori varijabilnosti mogu
biti demografske karakteristike, patološki ili genetički faktori. Pored toga, farmakokinetičke,
ali i farmakodinamičke interakcije mogu značajno doprineti varijabilnosti u odgovoru na lek.
Praćenje terapije antipsihotika klozapina i potencijalnih interakcija će biti prikazani na
populaciji odraslih pacijenata sa psihijatrijskim oboljenjem. Analiza potencijalnih interakcija
je urađena razmatrajući sve lekove koje su pacijenti primenjivali. Generalno,
farmakodinamičke interakcije mogu biti aditivne, sinergističke ili antagonističke. U
ispitivanoj populaciji često su opisivane interakcije u vezi sa pojačanim neželjenim dejstvom
klozapina. Od farmakokinetičkih interakcija, najčešće su one na nivou metabolizma usled
indukcije ili inhibicije citohrom P450 (CYP 450) izoenzima. Tako je uticaj valproinske
kiseline na metabolizam klozapina bio primećen u nekoliko situacija. Dalja analiza TDM
podataka doprinosi sagledavanju uticaja ovog antiepileptika na koncentraciju klozapina.
Praćenje varijabilnosti lekova predstavlja osnovu za optimizaciju terapije psihijatrijskih
oboljenja. U saradnji sa drugim zdravstvenim radnicima, farmaceuti imaju značajnu ulogu u
optimizaciji režima doziranja lekova, posebno u prevenciji i rešavanju lek-lek interakcija.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Monitoring drug variability in optimizing the treatment of psychiatric disorders
T1  - Praćenje varijabilnosti lekova u optimizaciji terapije psihijatrijskih oboljenja
VL  - 72
IS  - 4 suplement
SP  - S44
EP  - S45
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4442
ER  - 

@conference{
author = "Jovanović, Marija",
year = "2022",
abstract = "Psychiatric disorders significantly contribute to the overall burden of diseases in the
world's population. Antipsychotic drug therapy is the main treatment for patients with
schizophrenia or psychosis. These drugs show great variability in pharmacokinetic
characteristics, and consequently in drug level and therapeutic response. Therefore,
Therapeutic Drug Monitoring (TDM) is recommended for many drugs from this group (1).
Sources of variability can be demographic characteristics, pathological or genetic factors.
Moreover, pharmacokinetic, but also pharmacodynamic interactions may significantly
contribute to the variability in drug response. Monitoring of clozapine antipsychotic therapy
and potential interactions will be presented on the adult psychiatric patients. The analysis of
potential drug-drug interactions was performed considering all administered drugs. In
general, pharmacodynamic interactions may cause additive, synergistic, or antagonistic
effects between drugs. In the study population, interactions related to enhanced adverse
effect of clozapine have often been described. Regarding pharmacokinetic interactions, the
most common are those related to the induction or inhibition of cytochrome P450 (CYP 450)
metabolic isoenzymes. Hence, the effect of valproic acid on clozapine metabolism has been
detected in several occasions. Further analysis of TDM data contributes to the understanding
of the effect of this antiepileptic drug on clozapine levels. Monitoring drug variability is the
basis for optimizing the treatment of psychiatric disorders. In collaboration with other
health care professionals, pharmacists have a significant role in dosing optimization,
especially in the prevention and management of drug-drug interactions., Psihijatrijska oboljenja u značajnoj meri doprinose ukupnom opterećenju bolesti
svetske populacije. Antipsihotici su osnovni lekovi u terapiji shizofrenije i psihoza. Ovi lekovi
pokazuju veliku varijabilnost u farmakokinetičkim karakteristikama, a samim tim i u
koncentraciji i terapijskom odgovoru. Stoga je terapijsko praćenje lekova (Therapeutic Drug
Monitoring, TDM) preporučeno za mnoge lekove iz ove grupe (1). Izvori varijabilnosti mogu
biti demografske karakteristike, patološki ili genetički faktori. Pored toga, farmakokinetičke,
ali i farmakodinamičke interakcije mogu značajno doprineti varijabilnosti u odgovoru na lek.
Praćenje terapije antipsihotika klozapina i potencijalnih interakcija će biti prikazani na
populaciji odraslih pacijenata sa psihijatrijskim oboljenjem. Analiza potencijalnih interakcija
je urađena razmatrajući sve lekove koje su pacijenti primenjivali. Generalno,
farmakodinamičke interakcije mogu biti aditivne, sinergističke ili antagonističke. U
ispitivanoj populaciji često su opisivane interakcije u vezi sa pojačanim neželjenim dejstvom
klozapina. Od farmakokinetičkih interakcija, najčešće su one na nivou metabolizma usled
indukcije ili inhibicije citohrom P450 (CYP 450) izoenzima. Tako je uticaj valproinske
kiseline na metabolizam klozapina bio primećen u nekoliko situacija. Dalja analiza TDM
podataka doprinosi sagledavanju uticaja ovog antiepileptika na koncentraciju klozapina.
Praćenje varijabilnosti lekova predstavlja osnovu za optimizaciju terapije psihijatrijskih
oboljenja. U saradnji sa drugim zdravstvenim radnicima, farmaceuti imaju značajnu ulogu u
optimizaciji režima doziranja lekova, posebno u prevenciji i rešavanju lek-lek interakcija.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Monitoring drug variability in optimizing the treatment of psychiatric disorders, Praćenje varijabilnosti lekova u optimizaciji terapije psihijatrijskih oboljenja",
volume = "72",
number = "4 suplement",
pages = "S44-S45",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4442"
}

Jovanović, M.. (2022). Monitoring drug variability in optimizing the treatment of psychiatric disorders. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S44-S45.
https://hdl.handle.net/21.15107/rcub_farfar_4442

Jovanović M. Monitoring drug variability in optimizing the treatment of psychiatric disorders. in Arhiv za farmaciju. 2022;72(4 suplement):S44-S45.
https://hdl.handle.net/21.15107/rcub_farfar_4442 .

Jovanović, Marija, "Monitoring drug variability in optimizing the treatment of psychiatric disorders" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S44-S45,
https://hdl.handle.net/21.15107/rcub_farfar_4442 .

TY  - JOUR
AU  - Jovanović, Marija
AU  - Vučićević, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4303
AB  - Optimizing the dosing of medicines for pediatric patients in routine clinical practice and determining the dose for clinical trials is still a challenging task. Children differ from adults in their response to drugs due to inherent differences in pharmacokinetics and/or pharmacodynamics, and responses may also vary among pediatric patients of different ages. However, the greatest disparities compared to adult pharmacokinetic profiles are observed in children below 2 years of age. The maturation of the liver and the kidneys, as well as the variation in body composition, are considered to be the main sources of pharmacokinetic variability. Hence, besides specific pharmacodynamic features, understanding age-related changes in drug absorption, distribution, and elimination is fundamental for optimizing drug efficacy and avoiding toxicity. This paper summarizes the pharmacokinetic changes throughout the childhood, along with the effect of developmental changes on drug dosage calculation. In clinical practice, age and body weight-based dosing regimens are usually used. In spite of dosing recommendations based on age and/or body weight, variabilities in pharmacokinetics and pharmacodynamic response remain, implying a need to monitor patients and optimize the dosing regimen according to physiological characteristics, disease characteristics and therapy.
AB  - Optimizacija doziranja lekova kod pedijatrijskih pacijenata u rutinskoj kliničkoj praksi i procena doze pre započinjanja kliničkih studija je i dalje značajan izazov. Pedijatrijska populacija se razlikuje od odraslih pacijenata u odgovoru na lekove, što je uzrokovano izmenjenom farmakokinetikom i/ili farmakodinamikom, a odgovor može varirati i među decom različitog uzrasta. Međutim, najveće razlike u odnosu na farmakokinetičke profile odraslih pacijenata primećuju se kod dece mlađe od 2 godine. Sazrevanje jetre i bubrega, kao i promene u udelu telesnih tečenosti i masnog tkiva u odnosu na ukupnu telesnu masu, smatraju se glavnim izvorima farmakokinetičke varijabilnosti. Dakle, pored specifičnih farmakodinamičkih karakteristika, razumevanje razvojnih promena u resorpciji, raspodeli i eliminaciji leka je fundamentalno za optimizaciju efikasnosti i bezbednosti terapije. Ovaj rad sumira farmakokinetičke promene tokom detinjstva, zajedno sa uticajem razvojnih promena na izračunavanje doze leka. U kliničkoj praksi se obično koriste režimi doziranja zasnovani na starosti i telesnoj masi. Uprkos preporukama za doziranje na osnovu godina i/ili telesne mase, i dalje se uočava varijabilnost u farmakokinetici i farmakodinamičkom odgovoru, što ukazuje na potrebu za praćenjem pacijenata i optimizacijom režima doziranja prema fiziološkim karakteristikama, karakteristikama bolesti i terapiji.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Pediatric pharmacokinetic considerations and implications for drug dosing
T1  - Značaj farmakokinetike u doziranju lekova kod pedijatrijskih pacijenata
VL  - 72
IS  - 3
SP  - 340
EP  - 352
DO  - 10.5937/arhfarm72-37605
ER  - 

@article{
author = "Jovanović, Marija and Vučićević, Katarina",
year = "2022",
abstract = "Optimizing the dosing of medicines for pediatric patients in routine clinical practice and determining the dose for clinical trials is still a challenging task. Children differ from adults in their response to drugs due to inherent differences in pharmacokinetics and/or pharmacodynamics, and responses may also vary among pediatric patients of different ages. However, the greatest disparities compared to adult pharmacokinetic profiles are observed in children below 2 years of age. The maturation of the liver and the kidneys, as well as the variation in body composition, are considered to be the main sources of pharmacokinetic variability. Hence, besides specific pharmacodynamic features, understanding age-related changes in drug absorption, distribution, and elimination is fundamental for optimizing drug efficacy and avoiding toxicity. This paper summarizes the pharmacokinetic changes throughout the childhood, along with the effect of developmental changes on drug dosage calculation. In clinical practice, age and body weight-based dosing regimens are usually used. In spite of dosing recommendations based on age and/or body weight, variabilities in pharmacokinetics and pharmacodynamic response remain, implying a need to monitor patients and optimize the dosing regimen according to physiological characteristics, disease characteristics and therapy., Optimizacija doziranja lekova kod pedijatrijskih pacijenata u rutinskoj kliničkoj praksi i procena doze pre započinjanja kliničkih studija je i dalje značajan izazov. Pedijatrijska populacija se razlikuje od odraslih pacijenata u odgovoru na lekove, što je uzrokovano izmenjenom farmakokinetikom i/ili farmakodinamikom, a odgovor može varirati i među decom različitog uzrasta. Međutim, najveće razlike u odnosu na farmakokinetičke profile odraslih pacijenata primećuju se kod dece mlađe od 2 godine. Sazrevanje jetre i bubrega, kao i promene u udelu telesnih tečenosti i masnog tkiva u odnosu na ukupnu telesnu masu, smatraju se glavnim izvorima farmakokinetičke varijabilnosti. Dakle, pored specifičnih farmakodinamičkih karakteristika, razumevanje razvojnih promena u resorpciji, raspodeli i eliminaciji leka je fundamentalno za optimizaciju efikasnosti i bezbednosti terapije. Ovaj rad sumira farmakokinetičke promene tokom detinjstva, zajedno sa uticajem razvojnih promena na izračunavanje doze leka. U kliničkoj praksi se obično koriste režimi doziranja zasnovani na starosti i telesnoj masi. Uprkos preporukama za doziranje na osnovu godina i/ili telesne mase, i dalje se uočava varijabilnost u farmakokinetici i farmakodinamičkom odgovoru, što ukazuje na potrebu za praćenjem pacijenata i optimizacijom režima doziranja prema fiziološkim karakteristikama, karakteristikama bolesti i terapiji.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Pediatric pharmacokinetic considerations and implications for drug dosing, Značaj farmakokinetike u doziranju lekova kod pedijatrijskih pacijenata",
volume = "72",
number = "3",
pages = "340-352",
doi = "10.5937/arhfarm72-37605"
}

Jovanović, M.,& Vučićević, K.. (2022). Pediatric pharmacokinetic considerations and implications for drug dosing. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(3), 340-352.
https://doi.org/10.5937/arhfarm72-37605

Jovanović M, Vučićević K. Pediatric pharmacokinetic considerations and implications for drug dosing. in Arhiv za farmaciju. 2022;72(3):340-352.
doi:10.5937/arhfarm72-37605 .

Jovanović, Marija, Vučićević, Katarina, "Pediatric pharmacokinetic considerations and implications for drug dosing" in Arhiv za farmaciju, 72, no. 3 (2022):340-352,
https://doi.org/10.5937/arhfarm72-37605 . .

TY  - JOUR
AU  - Roganović, Maša
AU  - Homšek, Ana
AU  - Jovanović, Marija
AU  - Topić-Vučenović, Valentina
AU  - Ćulafić, Milica
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3960
AB  - Due to frequent clinical trial failures and consequently fewer new drug approvals, the need
for improvement in drug development has, to a certain extent, been met using model-based drug
development. Pharmacometrics is a part of pharmacology that quantifies drug behaviour,
treatment response and disease progression based on different models (pharmacokinetic - PK,
pharmacodynamic - PD, PK/PD models, etc.) and simulations. Regulatory bodies (European
Medicines Agency, Food and Drug Administration) encourage the use of modelling and
simulations to facilitate decision-making throughout all drug development phases. Moreover, the
identification of factors that contribute to variability provides a basis for dose individualisation in
routine clinical practice. This review summarises current knowledge regarding the application of
pharmacometrics in drug development and clinical practice with emphasis on the population
modelling approach.
AB  - Usled čestih neuspeha u kliničkim ispitivanjima i posledično manjeg broja odobrenja novih lekova, potreba za poboljšanjem u razvoju lekova je u određenoj meri zadovoljena korišćenjem pristupa razvoja lekova zasnovanog na modelu. Farmakometrija predstavlja granu farmakologije koja kvantifikuje ponašanje leka, odgovor na terapiju i napredovanje bolesti na osnovu različitih modela (farmakokinetički - FK, farmakodinamički - FD, FK/FD modeli itd.) i simulacija. Regulatorna tela (Evropska agencija za lekove, Uprava za hranu i lekove) podstiču primenu modelovanja i simulacija u svrhu lakšeg donošenja odluka tokom svih faza razvoja lekova. Štaviše, identifikacija faktora koji doprinose varijabilnosti predstavlja osnovu za individualizaciju doze u rutinskoj kliničkoj praksi. Ovaj revijalni rad sumira trenutno znanje u vezi sa primenom farmakometrije u razvoju lekova i kliničkoj praksi sa fokusom na populacionu analizu.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Concept and utility of population pharmacokinetic and pharmacokinetic/ pharmacodynamic models in drug development and clinical practice
T1  - Koncept i upotreba populacionih farmakokinetičkih i farmakokinetičko/farmakodinamičkih modela u razvoju leka i kliničkoj praksi
VL  - 71
IS  - 4
SP  - 336
EP  - 353
DO  - 10.5937/arhfarm71-32901
ER  - 

@article{
author = "Roganović, Maša and Homšek, Ana and Jovanović, Marija and Topić-Vučenović, Valentina and Ćulafić, Milica and Miljković, Branislava and Vučićević, Katarina",
year = "2021",
abstract = "Due to frequent clinical trial failures and consequently fewer new drug approvals, the need
for improvement in drug development has, to a certain extent, been met using model-based drug
development. Pharmacometrics is a part of pharmacology that quantifies drug behaviour,
treatment response and disease progression based on different models (pharmacokinetic - PK,
pharmacodynamic - PD, PK/PD models, etc.) and simulations. Regulatory bodies (European
Medicines Agency, Food and Drug Administration) encourage the use of modelling and
simulations to facilitate decision-making throughout all drug development phases. Moreover, the
identification of factors that contribute to variability provides a basis for dose individualisation in
routine clinical practice. This review summarises current knowledge regarding the application of
pharmacometrics in drug development and clinical practice with emphasis on the population
modelling approach., Usled čestih neuspeha u kliničkim ispitivanjima i posledično manjeg broja odobrenja novih lekova, potreba za poboljšanjem u razvoju lekova je u određenoj meri zadovoljena korišćenjem pristupa razvoja lekova zasnovanog na modelu. Farmakometrija predstavlja granu farmakologije koja kvantifikuje ponašanje leka, odgovor na terapiju i napredovanje bolesti na osnovu različitih modela (farmakokinetički - FK, farmakodinamički - FD, FK/FD modeli itd.) i simulacija. Regulatorna tela (Evropska agencija za lekove, Uprava za hranu i lekove) podstiču primenu modelovanja i simulacija u svrhu lakšeg donošenja odluka tokom svih faza razvoja lekova. Štaviše, identifikacija faktora koji doprinose varijabilnosti predstavlja osnovu za individualizaciju doze u rutinskoj kliničkoj praksi. Ovaj revijalni rad sumira trenutno znanje u vezi sa primenom farmakometrije u razvoju lekova i kliničkoj praksi sa fokusom na populacionu analizu.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Concept and utility of population pharmacokinetic and pharmacokinetic/ pharmacodynamic models in drug development and clinical practice, Koncept i upotreba populacionih farmakokinetičkih i farmakokinetičko/farmakodinamičkih modela u razvoju leka i kliničkoj praksi",
volume = "71",
number = "4",
pages = "336-353",
doi = "10.5937/arhfarm71-32901"
}

Roganović, M., Homšek, A., Jovanović, M., Topić-Vučenović, V., Ćulafić, M., Miljković, B.,& Vučićević, K.. (2021). Concept and utility of population pharmacokinetic and pharmacokinetic/ pharmacodynamic models in drug development and clinical practice. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 71(4), 336-353.
https://doi.org/10.5937/arhfarm71-32901

Roganović M, Homšek A, Jovanović M, Topić-Vučenović V, Ćulafić M, Miljković B, Vučićević K. Concept and utility of population pharmacokinetic and pharmacokinetic/ pharmacodynamic models in drug development and clinical practice. in Arhiv za farmaciju. 2021;71(4):336-353.
doi:10.5937/arhfarm71-32901 .

Roganović, Maša, Homšek, Ana, Jovanović, Marija, Topić-Vučenović, Valentina, Ćulafić, Milica, Miljković, Branislava, Vučićević, Katarina, "Concept and utility of population pharmacokinetic and pharmacokinetic/ pharmacodynamic models in drug development and clinical practice" in Arhiv za farmaciju, 71, no. 4 (2021):336-353,
https://doi.org/10.5937/arhfarm71-32901 . .

TY  - JOUR
AU  - Kovačević, Tijana
AU  - Miljković, Branislava
AU  - Kovačević, Peđa
AU  - Dragić, Saša
AU  - Momčićević, Danica
AU  - Avram, Sanja
AU  - Jovanović, Marija
AU  - Vučićević, Katarina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4826
AB  - Purpose: The present study aimed to establish a population pharmacokinetic model of vancomycin, including adult critically ill septic patients, with normal and impaired renal function.

Materials and methods: A prospective analysis of 146 concentrations from 73 adult critically ill septic patients treated with 1-h intravenous infusion of vancomycin were included in the study. A nonlinear mixed effects modeling (NONMEM) approach was applied for data analysis and evaluation of the final model. The influence of creatinine clearance calculated by the Cockcroft-Gault equation (CrCl), and other potential covariates on vancomycin clearance (CL) were evaluated.

Results: The final one-compartment pharmacokinetic model includes the effect of CrCl on CL. Population pharmacokinetic values for a typical subject were estimated at 0.024 l/h for CL dependent on renal function (CLCrCl), 1.93 l/h for residual portion of CL (not dependent on renal function), and 0.511 l/kg for volume of distribution (V). According to the final model, for patients with CrCl = 120 ml/min, the median vancomycin total CL is 4.81 l/h, while CrCl-dependent fraction accounts for approximately 60% of CL.

Conclusions: The developed population vancomycin model may be used in estimating individual CL for adult critically ill septic patients, and could be applied for individualizing dosage regimens taking into account the continuous effect of CrCl.
PB  - Elsevier Inc.
T2  - Journal of Critical Care
T1  - Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients
VL  - 55
SP  - 116
EP  - 121
DO  - 10.1016/j.jcrc.2019.10.012
ER  - 

@article{
author = "Kovačević, Tijana and Miljković, Branislava and Kovačević, Peđa and Dragić, Saša and Momčićević, Danica and Avram, Sanja and Jovanović, Marija and Vučićević, Katarina",
year = "2020",
abstract = "Purpose: The present study aimed to establish a population pharmacokinetic model of vancomycin, including adult critically ill septic patients, with normal and impaired renal function.

Materials and methods: A prospective analysis of 146 concentrations from 73 adult critically ill septic patients treated with 1-h intravenous infusion of vancomycin were included in the study. A nonlinear mixed effects modeling (NONMEM) approach was applied for data analysis and evaluation of the final model. The influence of creatinine clearance calculated by the Cockcroft-Gault equation (CrCl), and other potential covariates on vancomycin clearance (CL) were evaluated.

Results: The final one-compartment pharmacokinetic model includes the effect of CrCl on CL. Population pharmacokinetic values for a typical subject were estimated at 0.024 l/h for CL dependent on renal function (CLCrCl), 1.93 l/h for residual portion of CL (not dependent on renal function), and 0.511 l/kg for volume of distribution (V). According to the final model, for patients with CrCl = 120 ml/min, the median vancomycin total CL is 4.81 l/h, while CrCl-dependent fraction accounts for approximately 60% of CL.

Conclusions: The developed population vancomycin model may be used in estimating individual CL for adult critically ill septic patients, and could be applied for individualizing dosage regimens taking into account the continuous effect of CrCl.",
publisher = "Elsevier Inc.",
journal = "Journal of Critical Care",
title = "Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients",
volume = "55",
pages = "116-121",
doi = "10.1016/j.jcrc.2019.10.012"
}

Kovačević, T., Miljković, B., Kovačević, P., Dragić, S., Momčićević, D., Avram, S., Jovanović, M.,& Vučićević, K.. (2020). Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients. in Journal of Critical Care
Elsevier Inc.., 55, 116-121.
https://doi.org/10.1016/j.jcrc.2019.10.012

Kovačević T, Miljković B, Kovačević P, Dragić S, Momčićević D, Avram S, Jovanović M, Vučićević K. Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients. in Journal of Critical Care. 2020;55:116-121.
doi:10.1016/j.jcrc.2019.10.012 .

Kovačević, Tijana, Miljković, Branislava, Kovačević, Peđa, Dragić, Saša, Momčićević, Danica, Avram, Sanja, Jovanović, Marija, Vučićević, Katarina, "Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients" in Journal of Critical Care, 55 (2020):116-121,
https://doi.org/10.1016/j.jcrc.2019.10.012 . .