TY  - CONF
AU  - Topić Vučenović, Valentina
AU  - Rajkovača, Zvezdana
AU  - Jelić, Dijana
AU  - Stanimirović, Dragi
AU  - Mikov, Momir
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4820
AB  - Aim. The purpose of the study was to explore the influence of biologically effective dose (BED [Gy]), the administered radioactivity dose (Aa [MBq]), the total absorbed dose (ABD [Gy]), the maximum of absorbed dose-rate (MXR [Gy/h]) to radioactive iodine (131I) on the response in patients with benign thyroid disease.

Materials and methods. Data from adult patients with benign thyroid disease who had previously received a test dose of 131I activity were included in the analysis. Individual thyroid exposure parameters were estimated from the population biokinetic 131I model and the therapeutic activity doses (in range from 185 to 1300 MBq). Patients response was followed up at periodic intervals, starting from 4-6 weeks, up to one year after the administration of 131I. A successful clinical outcome was resolution of of hyperthyroidism. A population exposure-response analysis was performed using nonlinear mixed-effects modelling using NONMEM® (v. 7.4). The response data was modelled as ordered categorical with three levels (hyper-, eu- and hypothyroidism). The performance of the final model was evaluated using visual predictive check (VPC).

Results. In total 95 adult patients were analyzed, including 57 (60%) with Graves’ disease, 22 (23.2%) with toxic multinodular goiter and 16 (16.8%) with toxic adenoma. The probability of the outcome was best described by a proportional-odds model, including the log-linear model of 131I effect and the exponential model of the response-time relationship. Among all tested exposure measures, BED was included in the final model. Its inclusion in the base model was statistically significant (p<0.001). The value of 289.7 Gy was associated with 80% probability of successful treatment outcome one year after 131I application in patients with median thyroid volume of 32.28 mL.

Conclusion. The results indicate that using BED formalism could lead to a better individualisation of the therapy. The larger thyroid volume is associated with a lower probability of a successful outcome.

References.

    Topic Vucenovic V, Rajkovaca Z, Jelic D, Stanimirovic D, Vuleta G, Miljkovic B, Vucicevic K. Investigation of factors influencing radioiodine ((131)I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach. Eur J Clin Pharmacol. 2018;74(8):1037-1045.
    European Commission. Council Directive 2013/59/Euratom laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation, and repealing Directives 89/618/Euratom, 90/641/Euratom, 96/29/Euratom, 97/43/Euratom and 2003/122/Euratom (2014). Official Journal of the European Union L13/2014 57:1-73. doi:10.3000/19770677.L_2014.013.eng
    Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016;26(10):1343-1421.
PB  - PAGANZ
C3  - Population Approach Group of Australia & New Zeland Abstracts (PAGANZ)
T1  - The influence of biologically effective dose (BED) on the 131I therapy response in patients with benign thyroid disease – nonlinear mixed effect modelling approach
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4820
ER  - 

@conference{
author = "Topić Vučenović, Valentina and Rajkovača, Zvezdana and Jelić, Dijana and Stanimirović, Dragi and Mikov, Momir and Miljković, Branislava and Vučićević, Katarina",
year = "2021",
abstract = "Aim. The purpose of the study was to explore the influence of biologically effective dose (BED [Gy]), the administered radioactivity dose (Aa [MBq]), the total absorbed dose (ABD [Gy]), the maximum of absorbed dose-rate (MXR [Gy/h]) to radioactive iodine (131I) on the response in patients with benign thyroid disease.

Materials and methods. Data from adult patients with benign thyroid disease who had previously received a test dose of 131I activity were included in the analysis. Individual thyroid exposure parameters were estimated from the population biokinetic 131I model and the therapeutic activity doses (in range from 185 to 1300 MBq). Patients response was followed up at periodic intervals, starting from 4-6 weeks, up to one year after the administration of 131I. A successful clinical outcome was resolution of of hyperthyroidism. A population exposure-response analysis was performed using nonlinear mixed-effects modelling using NONMEM® (v. 7.4). The response data was modelled as ordered categorical with three levels (hyper-, eu- and hypothyroidism). The performance of the final model was evaluated using visual predictive check (VPC).

Results. In total 95 adult patients were analyzed, including 57 (60%) with Graves’ disease, 22 (23.2%) with toxic multinodular goiter and 16 (16.8%) with toxic adenoma. The probability of the outcome was best described by a proportional-odds model, including the log-linear model of 131I effect and the exponential model of the response-time relationship. Among all tested exposure measures, BED was included in the final model. Its inclusion in the base model was statistically significant (p<0.001). The value of 289.7 Gy was associated with 80% probability of successful treatment outcome one year after 131I application in patients with median thyroid volume of 32.28 mL.

Conclusion. The results indicate that using BED formalism could lead to a better individualisation of the therapy. The larger thyroid volume is associated with a lower probability of a successful outcome.

References.

    Topic Vucenovic V, Rajkovaca Z, Jelic D, Stanimirovic D, Vuleta G, Miljkovic B, Vucicevic K. Investigation of factors influencing radioiodine ((131)I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach. Eur J Clin Pharmacol. 2018;74(8):1037-1045.
    European Commission. Council Directive 2013/59/Euratom laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation, and repealing Directives 89/618/Euratom, 90/641/Euratom, 96/29/Euratom, 97/43/Euratom and 2003/122/Euratom (2014). Official Journal of the European Union L13/2014 57:1-73. doi:10.3000/19770677.L_2014.013.eng
    Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016;26(10):1343-1421.",
publisher = "PAGANZ",
journal = "Population Approach Group of Australia & New Zeland Abstracts (PAGANZ)",
title = "The influence of biologically effective dose (BED) on the 131I therapy response in patients with benign thyroid disease – nonlinear mixed effect modelling approach",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4820"
}

Topić Vučenović, V., Rajkovača, Z., Jelić, D., Stanimirović, D., Mikov, M., Miljković, B.,& Vučićević, K.. (2021). The influence of biologically effective dose (BED) on the 131I therapy response in patients with benign thyroid disease – nonlinear mixed effect modelling approach. in Population Approach Group of Australia & New Zeland Abstracts (PAGANZ)
PAGANZ..
https://hdl.handle.net/21.15107/rcub_farfar_4820

Topić Vučenović V, Rajkovača Z, Jelić D, Stanimirović D, Mikov M, Miljković B, Vučićević K. The influence of biologically effective dose (BED) on the 131I therapy response in patients with benign thyroid disease – nonlinear mixed effect modelling approach. in Population Approach Group of Australia & New Zeland Abstracts (PAGANZ). 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_4820 .

Topić Vučenović, Valentina, Rajkovača, Zvezdana, Jelić, Dijana, Stanimirović, Dragi, Mikov, Momir, Miljković, Branislava, Vučićević, Katarina, "The influence of biologically effective dose (BED) on the 131I therapy response in patients with benign thyroid disease – nonlinear mixed effect modelling approach" in Population Approach Group of Australia & New Zeland Abstracts (PAGANZ) (2021),
https://hdl.handle.net/21.15107/rcub_farfar_4820 .

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  - Topić-Vučenović, Valentina
AU  - Rajkovača, Zvezdana
AU  - Jelić, Dijana
AU  - Stanimirović, Dragi
AU  - Mikov, Momir
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3927
AB  - Purpose: The study aimed to explore the relationship of different exposure measures with 131I therapy response in patients with benign thyroid disease, estimate the variability in the response, investigate possible covariates, and discuss dosing implications of the results. Methods: A population exposure-response analysis was performed using nonlinear mixed-effects modelling. Data from 95 adult patients with benign thyroid disease were analysed. Evaluated exposure parameters were: administered radioactivity dose (Aa) [MBq], total absorbed dose (ABD) [Gy], maximum of absorbed dose-rate (MXR) [Gy/h] and biologically effective dose (BED) [Gy]. The response was modelled as ordered categorical data: hyper-, eu- and hypothyroidism. The final model performance was evaluated by a visual predictive check. Results: The probability of the outcome following 131I therapy was best described by a proportional-odds model, including the log-linear model of 131I effect and the exponential model of the response-time relationship. All exposure measures were statistically significant with p<0.001, with BED and ABD being statistically better than the other two. Nevertheless, as BED resulted in the lowest AIC value, it was included in the final model. Accordingly, BED value of 289.7 Gy is associated with 80% probability of successful treatment outcome 12 months after 131I application in patients with median thyroid volume (32.28 mL). The target thyroid volume was a statistically significant covariate. The visual predictive check of the final model showed good model performance. Conclusion: Our results imply that BED formalism could aid in therapy individualisation. The larger thyroid volume is associated with a lower probability of a successful outcome.
PB  - Elsevier B.V.
T2  - European Journal of Pharmaceutical Sciences
T1  - Population exposure-response model of 131I in patients with benign thyroid disease
VL  - 165
DO  - 10.1016/j.ejps.2021.105942
ER  - 

@article{
author = "Topić-Vučenović, Valentina and Rajkovača, Zvezdana and Jelić, Dijana and Stanimirović, Dragi and Mikov, Momir and Miljković, Branislava and Vučićević, Katarina",
year = "2021",
abstract = "Purpose: The study aimed to explore the relationship of different exposure measures with 131I therapy response in patients with benign thyroid disease, estimate the variability in the response, investigate possible covariates, and discuss dosing implications of the results. Methods: A population exposure-response analysis was performed using nonlinear mixed-effects modelling. Data from 95 adult patients with benign thyroid disease were analysed. Evaluated exposure parameters were: administered radioactivity dose (Aa) [MBq], total absorbed dose (ABD) [Gy], maximum of absorbed dose-rate (MXR) [Gy/h] and biologically effective dose (BED) [Gy]. The response was modelled as ordered categorical data: hyper-, eu- and hypothyroidism. The final model performance was evaluated by a visual predictive check. Results: The probability of the outcome following 131I therapy was best described by a proportional-odds model, including the log-linear model of 131I effect and the exponential model of the response-time relationship. All exposure measures were statistically significant with p<0.001, with BED and ABD being statistically better than the other two. Nevertheless, as BED resulted in the lowest AIC value, it was included in the final model. Accordingly, BED value of 289.7 Gy is associated with 80% probability of successful treatment outcome 12 months after 131I application in patients with median thyroid volume (32.28 mL). The target thyroid volume was a statistically significant covariate. The visual predictive check of the final model showed good model performance. Conclusion: Our results imply that BED formalism could aid in therapy individualisation. The larger thyroid volume is associated with a lower probability of a successful outcome.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Population exposure-response model of 131I in patients with benign thyroid disease",
volume = "165",
doi = "10.1016/j.ejps.2021.105942"
}

Topić-Vučenović, V., Rajkovača, Z., Jelić, D., Stanimirović, D., Mikov, M., Miljković, B.,& Vučićević, K.. (2021). Population exposure-response model of 131I in patients with benign thyroid disease. in European Journal of Pharmaceutical Sciences
Elsevier B.V.., 165.
https://doi.org/10.1016/j.ejps.2021.105942

Topić-Vučenović V, Rajkovača Z, Jelić D, Stanimirović D, Mikov M, Miljković B, Vučićević K. Population exposure-response model of 131I in patients with benign thyroid disease. in European Journal of Pharmaceutical Sciences. 2021;165.
doi:10.1016/j.ejps.2021.105942 .

Topić-Vučenović, Valentina, Rajkovača, Zvezdana, Jelić, Dijana, Stanimirović, Dragi, Mikov, Momir, Miljković, Branislava, Vučićević, Katarina, "Population exposure-response model of 131I in patients with benign thyroid disease" in European Journal of Pharmaceutical Sciences, 165 (2021),
https://doi.org/10.1016/j.ejps.2021.105942 . .

TY  - JOUR
AU  - Vezmar-Kovačević, Sandra
AU  - Vučićević, Katarina
AU  - Topić-Vučenović, Valentina
AU  - Rajkovača, Zvezdana
AU  - Miljković, Branislava
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3269
AB  - Patients often seek advise from doctors and pharmacists about pain treatment. Opioid and non-opioid analgesics are the most commonly used drugs in the treatment of pain, but they have potential for pharmacodynamic and pharmacokinetic drug-drug interactions. The risk of central nervous system depression and respiratory depression is increased if opioid analgesics are used with anxiolytics, first-generation antihistamines, and antidepressants. Serotonin syndrome can occur if tramadol and fentanyl are used with selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline inhibitors, monoamino oxidase inhibitors, etc. Decreased elimination of opioid analgesics as a consequence of CYP2D6 and CYP3A4 isoenzyme inhibition can result in their increased efficacy but sedation and respiratory depression have also been reported. Caution is needed when non-steroidal anti-inflammatory drugs (NSAIDs) are used concomitantly with other drugs that cause bleeding such as anticoagulants and SSRIs or drugs that decrease the elimination of NSAIDs by inhibition of CYP2C9. NSAIDs can antagonize the effect of antihypertensives, and interaction with angiotensin-converting enzyme inhibitors may result in renal failure. In comparison with opioid analgesics and NSAIDs, paracetamol has the lowest potential for clinically significant interactions. The prophylactic administration of paracetamol after vaccination should be avoided and patients should be advised not to use alcohol during therapy.
AB  - Pacijenti se često obraćaju lekarima i farmaceutima za pomoć u terapiji bola. Opioidni i neopioidni analgetici su najčešće lekovi izbora u terapiji bola ali imaju veliki potencijal za stupanje u farmakodinamske i farmakokinetičke interakcije sa drugim lekovima. Kod opioidnih analgetika povećan je rizik od pojave depresije centralnog nervnog sistema i respiratorne depresije ukoliko se ovi lekovi primenjuju sa anksioliticima, antihistaminicima prve generacije i antidepresivima. Serotoninski sindrom se može javiti ukoliko se tramadol i fentanil primenjuju sa selektivnim inhibitorima preuzimanja serotonina (SSRI), inhibitorima preuzimanja serotonina i noradrenalina, inhibitorima monoamino-oksidaze i dr. Usporena eliminacija opioidnih analgetika, kao posledica inhibicije izoenzima CYP2D6 i CYP3A4 može rezultirati njihovom povećanom efikasnošću ali i pojavom sedacije i respiratorne depresije. Oprez je potreban kada se nesteroidni antiinflamatorni lekovi (NSAIL) primenjuju istovremeno sa drugim lekovima koji mogu dovesti do krvarenja poput antikoagulanasa i SSRI ili lekovima koji usporavaju eliminaciju NSAIL inhibicijom izoenzima CYP2C9. NSAIL mogu antagonizovati dejstvo antihipertenziva, a interakcija sa inhibitorima angiotenzin-konvertujućeg enzima može rezultirati bubrežnom insuficijencijom. U poređenju sa opioidnim analgeticima i NSAIL, paracetamol ima najmanji potencijal za stupanje u klinički značajne interakcije. Potrebno je izbegavati profilaktičku primenu paracetamola nakon vakcinacije i skrenuti pacijentima pažnju da ne primenjuju alkohol u toku terapije.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Clinically important drug interactions with opioid and non-opioid analgesics
T1  - Klinički značajne interakcije opioidnih i neopioidnih analgetika
VL  - 69
IS  - 1
SP  - 1071
EP  - 1083
DO  - 10.5937/ArhFarm1901071V
ER  - 

@article{
author = "Vezmar-Kovačević, Sandra and Vučićević, Katarina and Topić-Vučenović, Valentina and Rajkovača, Zvezdana and Miljković, Branislava",
year = "2019",
abstract = "Patients often seek advise from doctors and pharmacists about pain treatment. Opioid and non-opioid analgesics are the most commonly used drugs in the treatment of pain, but they have potential for pharmacodynamic and pharmacokinetic drug-drug interactions. The risk of central nervous system depression and respiratory depression is increased if opioid analgesics are used with anxiolytics, first-generation antihistamines, and antidepressants. Serotonin syndrome can occur if tramadol and fentanyl are used with selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline inhibitors, monoamino oxidase inhibitors, etc. Decreased elimination of opioid analgesics as a consequence of CYP2D6 and CYP3A4 isoenzyme inhibition can result in their increased efficacy but sedation and respiratory depression have also been reported. Caution is needed when non-steroidal anti-inflammatory drugs (NSAIDs) are used concomitantly with other drugs that cause bleeding such as anticoagulants and SSRIs or drugs that decrease the elimination of NSAIDs by inhibition of CYP2C9. NSAIDs can antagonize the effect of antihypertensives, and interaction with angiotensin-converting enzyme inhibitors may result in renal failure. In comparison with opioid analgesics and NSAIDs, paracetamol has the lowest potential for clinically significant interactions. The prophylactic administration of paracetamol after vaccination should be avoided and patients should be advised not to use alcohol during therapy., Pacijenti se često obraćaju lekarima i farmaceutima za pomoć u terapiji bola. Opioidni i neopioidni analgetici su najčešće lekovi izbora u terapiji bola ali imaju veliki potencijal za stupanje u farmakodinamske i farmakokinetičke interakcije sa drugim lekovima. Kod opioidnih analgetika povećan je rizik od pojave depresije centralnog nervnog sistema i respiratorne depresije ukoliko se ovi lekovi primenjuju sa anksioliticima, antihistaminicima prve generacije i antidepresivima. Serotoninski sindrom se može javiti ukoliko se tramadol i fentanil primenjuju sa selektivnim inhibitorima preuzimanja serotonina (SSRI), inhibitorima preuzimanja serotonina i noradrenalina, inhibitorima monoamino-oksidaze i dr. Usporena eliminacija opioidnih analgetika, kao posledica inhibicije izoenzima CYP2D6 i CYP3A4 može rezultirati njihovom povećanom efikasnošću ali i pojavom sedacije i respiratorne depresije. Oprez je potreban kada se nesteroidni antiinflamatorni lekovi (NSAIL) primenjuju istovremeno sa drugim lekovima koji mogu dovesti do krvarenja poput antikoagulanasa i SSRI ili lekovima koji usporavaju eliminaciju NSAIL inhibicijom izoenzima CYP2C9. NSAIL mogu antagonizovati dejstvo antihipertenziva, a interakcija sa inhibitorima angiotenzin-konvertujućeg enzima može rezultirati bubrežnom insuficijencijom. U poređenju sa opioidnim analgeticima i NSAIL, paracetamol ima najmanji potencijal za stupanje u klinički značajne interakcije. Potrebno je izbegavati profilaktičku primenu paracetamola nakon vakcinacije i skrenuti pacijentima pažnju da ne primenjuju alkohol u toku terapije.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Clinically important drug interactions with opioid and non-opioid analgesics, Klinički značajne interakcije opioidnih i neopioidnih analgetika",
volume = "69",
number = "1",
pages = "1071-1083",
doi = "10.5937/ArhFarm1901071V"
}

Vezmar-Kovačević, S., Vučićević, K., Topić-Vučenović, V., Rajkovača, Z.,& Miljković, B.. (2019). Clinically important drug interactions with opioid and non-opioid analgesics. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 69(1), 1071-1083.
https://doi.org/10.5937/ArhFarm1901071V

Vezmar-Kovačević S, Vučićević K, Topić-Vučenović V, Rajkovača Z, Miljković B. Clinically important drug interactions with opioid and non-opioid analgesics. in Arhiv za farmaciju. 2019;69(1):1071-1083.
doi:10.5937/ArhFarm1901071V .

Vezmar-Kovačević, Sandra, Vučićević, Katarina, Topić-Vučenović, Valentina, Rajkovača, Zvezdana, Miljković, Branislava, "Clinically important drug interactions with opioid and non-opioid analgesics" in Arhiv za farmaciju, 69, no. 1 (2019):1071-1083,
https://doi.org/10.5937/ArhFarm1901071V . .

TY  - JOUR
AU  - Topić-Vučenović, Valentina
AU  - Rajkovača, Zvezdana
AU  - Jelić, Dijana
AU  - Stanimirović, Dragi
AU  - Vuleta, Goran
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3207
AB  - Radioiodine (I-131) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize I-131 biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal I-131 kinetics by developing a population model. Population pharmacokinetic analysis was performed using a nonlinear mixed effects approach. Data sets of 345 adult patients with benign thyroid disease, retrospectively collected from patients' medical records, were evaluated in the analysis. The two-compartment model of I-131 biokinetics representing the blood compartment and thyroid gland was used as the structural model. Results of the study indicate that the rate constant of the uptake of I-131 into the thyroid (k (tu)) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT(4)), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of I-131 is affected by the age of the patients. Inclusion of the covariates in the base model resulted in a decrease of the between subject variability for k (tu) from 91 (3.9) to 53.9 (4.5)%. This is the first population model that accounts for the influence of fT(4) and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to I-131 and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.
PB  - Springer Heidelberg, Heidelberg
T2  - European Journal of Clinical Pharmacology
T1  - Investigation of factors influencing radioiodine (I-131) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach
VL  - 74
IS  - 8
SP  - 1037
EP  - 1045
DO  - 10.1007/s00228-018-2459-8
ER  - 

@article{
author = "Topić-Vučenović, Valentina and Rajkovača, Zvezdana and Jelić, Dijana and Stanimirović, Dragi and Vuleta, Goran and Miljković, Branislava and Vučićević, Katarina",
year = "2018",
abstract = "Radioiodine (I-131) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize I-131 biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal I-131 kinetics by developing a population model. Population pharmacokinetic analysis was performed using a nonlinear mixed effects approach. Data sets of 345 adult patients with benign thyroid disease, retrospectively collected from patients' medical records, were evaluated in the analysis. The two-compartment model of I-131 biokinetics representing the blood compartment and thyroid gland was used as the structural model. Results of the study indicate that the rate constant of the uptake of I-131 into the thyroid (k (tu)) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT(4)), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of I-131 is affected by the age of the patients. Inclusion of the covariates in the base model resulted in a decrease of the between subject variability for k (tu) from 91 (3.9) to 53.9 (4.5)%. This is the first population model that accounts for the influence of fT(4) and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to I-131 and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "European Journal of Clinical Pharmacology",
title = "Investigation of factors influencing radioiodine (I-131) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach",
volume = "74",
number = "8",
pages = "1037-1045",
doi = "10.1007/s00228-018-2459-8"
}

Topić-Vučenović, V., Rajkovača, Z., Jelić, D., Stanimirović, D., Vuleta, G., Miljković, B.,& Vučićević, K.. (2018). Investigation of factors influencing radioiodine (I-131) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach. in European Journal of Clinical Pharmacology
Springer Heidelberg, Heidelberg., 74(8), 1037-1045.
https://doi.org/10.1007/s00228-018-2459-8

Topić-Vučenović V, Rajkovača Z, Jelić D, Stanimirović D, Vuleta G, Miljković B, Vučićević K. Investigation of factors influencing radioiodine (I-131) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach. in European Journal of Clinical Pharmacology. 2018;74(8):1037-1045.
doi:10.1007/s00228-018-2459-8 .

Topić-Vučenović, Valentina, Rajkovača, Zvezdana, Jelić, Dijana, Stanimirović, Dragi, Vuleta, Goran, Miljković, Branislava, Vučićević, Katarina, "Investigation of factors influencing radioiodine (I-131) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach" in European Journal of Clinical Pharmacology, 74, no. 8 (2018):1037-1045,
https://doi.org/10.1007/s00228-018-2459-8 . .

TY  - CONF
AU  - Topić-Vučenović, Valentina
AU  - Vučićević, Katarina
AU  - Rajkovača, Zvezdana
AU  - Stanimirović, D.
AU  - Vuleta, Goran
AU  - Jelić, D.
AU  - Miljković, Branislava
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2924
PB  - Springer, New York
C3  - European Journal of Nuclear Medicine and Molecular Imaging
T1  - Investigation of influence of anti-thyroid drug discontinuation time on I-131 biokinetics in patients with benign thyroid disease
VL  - 44
IS  - Supplement 2
SP  - S809
EP  - S809
DO  - 10.1007/s00259-017-3822-1
ER  - 

@conference{
author = "Topić-Vučenović, Valentina and Vučićević, Katarina and Rajkovača, Zvezdana and Stanimirović, D. and Vuleta, Goran and Jelić, D. and Miljković, Branislava",
year = "2017",
publisher = "Springer, New York",
journal = "European Journal of Nuclear Medicine and Molecular Imaging",
title = "Investigation of influence of anti-thyroid drug discontinuation time on I-131 biokinetics in patients with benign thyroid disease",
volume = "44",
number = "Supplement 2",
pages = "S809-S809",
doi = "10.1007/s00259-017-3822-1"
}

Topić-Vučenović, V., Vučićević, K., Rajkovača, Z., Stanimirović, D., Vuleta, G., Jelić, D.,& Miljković, B.. (2017). Investigation of influence of anti-thyroid drug discontinuation time on I-131 biokinetics in patients with benign thyroid disease. in European Journal of Nuclear Medicine and Molecular Imaging
Springer, New York., 44(Supplement 2), S809-S809.
https://doi.org/10.1007/s00259-017-3822-1

Topić-Vučenović V, Vučićević K, Rajkovača Z, Stanimirović D, Vuleta G, Jelić D, Miljković B. Investigation of influence of anti-thyroid drug discontinuation time on I-131 biokinetics in patients with benign thyroid disease. in European Journal of Nuclear Medicine and Molecular Imaging. 2017;44(Supplement 2):S809-S809.
doi:10.1007/s00259-017-3822-1 .

Topić-Vučenović, Valentina, Vučićević, Katarina, Rajkovača, Zvezdana, Stanimirović, D., Vuleta, Goran, Jelić, D., Miljković, Branislava, "Investigation of influence of anti-thyroid drug discontinuation time on I-131 biokinetics in patients with benign thyroid disease" in European Journal of Nuclear Medicine and Molecular Imaging, 44, no. Supplement 2 (2017):S809-S809,
https://doi.org/10.1007/s00259-017-3822-1 . .

TY  - JOUR
AU  - Topić-Vučenović, Valentina
AU  - Rajkovača, Zvezdana
AU  - Vezmar-Kovačević, Sandra
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2812
AB  - Radioactive iodine represents the significant therapeutic option in the treatment of benign thyroid disease. Despite a decades-long experience and a large number of treated patients, many issues related to the therapy with radioactive iodine are still under discussion, including the method of therapeutic dose determination and the factors that affect the therapy outcome. Clinical practice, as well as recommendations of the relevant guidelines in terms of the dosing of radioactive iodine, vary widely in the world: from the fixed dose application to the complex dosimetric protocols. A greater presence of dosimetric approach would facilitate the establishment of dose-effect correlation and the study of influence of various factors on the therapy outcome. Development of the new dosing protocols, as well as new insights into factors that affect therapeutic outcome, enable further improvement of both efficacy and safety of the radioactive iodine therapy for an individual patient.
AB  - Radioaktivni jod predstavlja značajnu terapijsku opciju u liječenju benignih oboljenja štitaste žlijezde. Uprkos višedecenijskom iskustvu i velikom broju liječenih pacijenata, mnoga pitanja vezana za terapiju radioaktivnim jodom još su uvijek predmet diskusija, uključujući način određivanja terapijske doze, kao i faktore koji utiču na ishod terapije. Klinička praksa, kao i preporuke odgovarajućih vodiča u pogledu doziranja radioaktivnog joda široko variraju u svijetu, od primjene fiksnih doza do kompleksnih dozimetrijskih protokola. Veća zastupljenost dozimetrijskog pristupa olakšala bi uspostavljanje korelacije doza-efekat i proučavanje uticaja raznih faktora na ishod terapije. Razvoj novih protokola za izračunavanje terapijske doze aktivnosti, kao i nova saznanja o faktorima koji utiču na ishod terapije omogućavaju dalje unaprijeđenje kako efikasnosti, tako i bezbjednosti terapije radioaktivnim jodom za individualnog pacijenta.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Challenges and current views on dosing of radioactive iodine in the treatment of benign thyroid disease
T1  - Izazovi i stavovi o doziranju radioaktivnog joda u terapiji benignih oboljenja štitaste žlijezde
VL  - 67
IS  - 6
SP  - 333
EP  - 344
DO  - 10.5937/arhfarm1706333T
ER  - 

@article{
author = "Topić-Vučenović, Valentina and Rajkovača, Zvezdana and Vezmar-Kovačević, Sandra and Miljković, Branislava and Vučićević, Katarina",
year = "2017",
abstract = "Radioactive iodine represents the significant therapeutic option in the treatment of benign thyroid disease. Despite a decades-long experience and a large number of treated patients, many issues related to the therapy with radioactive iodine are still under discussion, including the method of therapeutic dose determination and the factors that affect the therapy outcome. Clinical practice, as well as recommendations of the relevant guidelines in terms of the dosing of radioactive iodine, vary widely in the world: from the fixed dose application to the complex dosimetric protocols. A greater presence of dosimetric approach would facilitate the establishment of dose-effect correlation and the study of influence of various factors on the therapy outcome. Development of the new dosing protocols, as well as new insights into factors that affect therapeutic outcome, enable further improvement of both efficacy and safety of the radioactive iodine therapy for an individual patient., Radioaktivni jod predstavlja značajnu terapijsku opciju u liječenju benignih oboljenja štitaste žlijezde. Uprkos višedecenijskom iskustvu i velikom broju liječenih pacijenata, mnoga pitanja vezana za terapiju radioaktivnim jodom još su uvijek predmet diskusija, uključujući način određivanja terapijske doze, kao i faktore koji utiču na ishod terapije. Klinička praksa, kao i preporuke odgovarajućih vodiča u pogledu doziranja radioaktivnog joda široko variraju u svijetu, od primjene fiksnih doza do kompleksnih dozimetrijskih protokola. Veća zastupljenost dozimetrijskog pristupa olakšala bi uspostavljanje korelacije doza-efekat i proučavanje uticaja raznih faktora na ishod terapije. Razvoj novih protokola za izračunavanje terapijske doze aktivnosti, kao i nova saznanja o faktorima koji utiču na ishod terapije omogućavaju dalje unaprijeđenje kako efikasnosti, tako i bezbjednosti terapije radioaktivnim jodom za individualnog pacijenta.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Challenges and current views on dosing of radioactive iodine in the treatment of benign thyroid disease, Izazovi i stavovi o doziranju radioaktivnog joda u terapiji benignih oboljenja štitaste žlijezde",
volume = "67",
number = "6",
pages = "333-344",
doi = "10.5937/arhfarm1706333T"
}

Topić-Vučenović, V., Rajkovača, Z., Vezmar-Kovačević, S., Miljković, B.,& Vučićević, K.. (2017). Challenges and current views on dosing of radioactive iodine in the treatment of benign thyroid disease. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 67(6), 333-344.
https://doi.org/10.5937/arhfarm1706333T

Topić-Vučenović V, Rajkovača Z, Vezmar-Kovačević S, Miljković B, Vučićević K. Challenges and current views on dosing of radioactive iodine in the treatment of benign thyroid disease. in Arhiv za farmaciju. 2017;67(6):333-344.
doi:10.5937/arhfarm1706333T .

Topić-Vučenović, Valentina, Rajkovača, Zvezdana, Vezmar-Kovačević, Sandra, Miljković, Branislava, Vučićević, Katarina, "Challenges and current views on dosing of radioactive iodine in the treatment of benign thyroid disease" in Arhiv za farmaciju, 67, no. 6 (2017):333-344,
https://doi.org/10.5937/arhfarm1706333T . .