TY  - THES
AU  - Golubović, Bojana C.
PY  - 2019
UR  - http://nardus.mpn.gov.rs/handle/123456789/11250
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=6811
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:19903/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=2048355426
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3689
AB  - Циљ докторске дисертације био је да се применом популационефармакокинетичке анализе идентификују и квантификују факторифармакокинетичке варијабилности такролимуса и сиролимуса у пацијената сатрансплантираним бубрегом.Сви коришћени подаци, укључујући измерене концентрације лекова, били су деоредовног терапијског и клиничког праћења пацијената. Популациона анализавршена је коришћењем софтвера NONMEM®. Подаци за такролимус за период до6 месеци и период од око годину дана након трансплантације анализирани сунезависно. Према критеријумима за укључивање/искључивање укупно је у групиза рани период након трансплантације било 105 пацијената, док је у групи запериод од око годину дана након трансплантације било 45 пацијената. Развијенимодели валидирани су техникама интерне валидације. Групу за развој модела засиролимус чинили су подаци 25 пацијената, док су подаци 13 пацијенатакоришћени за екстерну валидацију. Додатно, развијени модел за сиролимусвалидиран је и техникама интерне валидације.Као фактори фармакокинетичке варијабилности оралног клиренса (CL/F)такролимуса у првих 6 месеци након трансплантације идентификовани супротекло време од трансплантације, укупна телесна маса, хематокрит, нивоаспартат аминотрансферазе (АST) и укупни протеини плазме. На вредности CL/F упериоду од око годину дана након трансплантације значајно су утицали укупнателесна маса и дневна доза такролимуса. Део варијабилности у CL/F сиролимусаобјашњен је старошћу и функцијом јетре, израженом преко АST. Валидацијаразвијених модела показала је њихову стабилност и адекватну предиктабилност.Примена добијених валидираних модела омогућава израчунавање индивидуалнихвредности CL/F, параметра који је основ за индивидуализацију режима дозирања.
AB  - The aim of the doctoral dissertation was to identify and quantify factors of thepharmacokinetic variability of tacrolimus and sirolimus in patients with a transplantedkidney using the population pharmacokinetic analysis.All data used, including measured drug concentrations, were part of the regulartherapeutic and clinical monitoring of patients. Population analysis was performed usingNONMEM® software. Data for tacrolimus for a period of up to 6 months and a period ofabout a year after transplantation were analyzed independently. According to the criteriafor inclusion / exclusion, in the group for the early period after transplantation were 105patients, while in the group for the period of approximately one year after thetransplantаtion were 45 patients. Developed models are validated by internal validationtechniques. The sirolimus model was developed using data of 25 patients, while data of13 patients were used for external validation. In addition, the developed model forsirolimus was validated by internal validation techniques.The post-transplantation time, total body weight, hematocrit, aspartate aminotransferaselevel (AST) and total plasma proteins have been identified as factors of thepharmacokinetic variability of tacrolimus oral clearance (CL/F) in the first 6 monthsfollowing transplantation. On the other hand, the CL/F in the period of about a yearafter the transplantation were significantly influenced by the total body weight andtacrolimus daily dose. Part of the variability in sirolimus CL/F was explained by the ageand function of the liver, expressed through AST. The validation of the developedmodels has shown their stability and adequate predictability. The application of theobtained validated models allows estimation of individual CL/F, a parameter that is thebasis for dosing regimen individualization
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Популациони приступ фармакокинетичкој анализи такролимуса и сиролимуса у пацијената са трансплантираним бубрегом
UR  - https://hdl.handle.net/21.15107/rcub_nardus_11250
ER  - 

@phdthesis{
author = "Golubović, Bojana C.",
year = "2019",
abstract = "Циљ докторске дисертације био је да се применом популационефармакокинетичке анализе идентификују и квантификују факторифармакокинетичке варијабилности такролимуса и сиролимуса у пацијената сатрансплантираним бубрегом.Сви коришћени подаци, укључујући измерене концентрације лекова, били су деоредовног терапијског и клиничког праћења пацијената. Популациона анализавршена је коришћењем софтвера NONMEM®. Подаци за такролимус за период до6 месеци и период од око годину дана након трансплантације анализирани сунезависно. Према критеријумима за укључивање/искључивање укупно је у групиза рани период након трансплантације било 105 пацијената, док је у групи запериод од око годину дана након трансплантације било 45 пацијената. Развијенимодели валидирани су техникама интерне валидације. Групу за развој модела засиролимус чинили су подаци 25 пацијената, док су подаци 13 пацијенатакоришћени за екстерну валидацију. Додатно, развијени модел за сиролимусвалидиран је и техникама интерне валидације.Као фактори фармакокинетичке варијабилности оралног клиренса (CL/F)такролимуса у првих 6 месеци након трансплантације идентификовани супротекло време од трансплантације, укупна телесна маса, хематокрит, нивоаспартат аминотрансферазе (АST) и укупни протеини плазме. На вредности CL/F упериоду од око годину дана након трансплантације значајно су утицали укупнателесна маса и дневна доза такролимуса. Део варијабилности у CL/F сиролимусаобјашњен је старошћу и функцијом јетре, израженом преко АST. Валидацијаразвијених модела показала је њихову стабилност и адекватну предиктабилност.Примена добијених валидираних модела омогућава израчунавање индивидуалнихвредности CL/F, параметра који је основ за индивидуализацију режима дозирања., The aim of the doctoral dissertation was to identify and quantify factors of thepharmacokinetic variability of tacrolimus and sirolimus in patients with a transplantedkidney using the population pharmacokinetic analysis.All data used, including measured drug concentrations, were part of the regulartherapeutic and clinical monitoring of patients. Population analysis was performed usingNONMEM® software. Data for tacrolimus for a period of up to 6 months and a period ofabout a year after transplantation were analyzed independently. According to the criteriafor inclusion / exclusion, in the group for the early period after transplantation were 105patients, while in the group for the period of approximately one year after thetransplantаtion were 45 patients. Developed models are validated by internal validationtechniques. The sirolimus model was developed using data of 25 patients, while data of13 patients were used for external validation. In addition, the developed model forsirolimus was validated by internal validation techniques.The post-transplantation time, total body weight, hematocrit, aspartate aminotransferaselevel (AST) and total plasma proteins have been identified as factors of thepharmacokinetic variability of tacrolimus oral clearance (CL/F) in the first 6 monthsfollowing transplantation. On the other hand, the CL/F in the period of about a yearafter the transplantation were significantly influenced by the total body weight andtacrolimus daily dose. Part of the variability in sirolimus CL/F was explained by the ageand function of the liver, expressed through AST. The validation of the developedmodels has shown their stability and adequate predictability. The application of theobtained validated models allows estimation of individual CL/F, a parameter that is thebasis for dosing regimen individualization",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Популациони приступ фармакокинетичкој анализи такролимуса и сиролимуса у пацијената са трансплантираним бубрегом",
url = "https://hdl.handle.net/21.15107/rcub_nardus_11250"
}

Golubović, B. C.. (2019). Популациони приступ фармакокинетичкој анализи такролимуса и сиролимуса у пацијената са трансплантираним бубрегом. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_11250

Golubović BC. Популациони приступ фармакокинетичкој анализи такролимуса и сиролимуса у пацијената са трансплантираним бубрегом. in Универзитет у Београду. 2019;.
https://hdl.handle.net/21.15107/rcub_nardus_11250 .

Golubović, Bojana C., "Популациони приступ фармакокинетичкој анализи такролимуса и сиролимуса у пацијената са трансплантираним бубрегом" in Универзитет у Београду (2019),
https://hdl.handle.net/21.15107/rcub_nardus_11250 .

TY  - JOUR
AU  - Rakić-Ignjatović, Anita
AU  - Miljković, Branislava
AU  - Todorović, Dejan
AU  - Timotijević, Ivana
AU  - Pokrajac, Milena
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1518
AB  - Because moclobemide pharmacokinetics vary considerably among individuals, monitoring of plasma concentrations lends insight into its pharmacokinetic behavior and enhances its rational use in clinical practice. The aim of this study was to evaluate whether single concentration-time points could adequately predict moclobemide systemic exposure. Pharmacokinetic data (full 7-point pharmacokinetic profiles), obtained from 21 depressive inpatients receiving moclobemide (150 mg 3 times daily), were randomly split into development (n = 18) and validation (n = 16) sets. Correlations between the single concentration-time points and the area under the concentration-time curve within a 6-hour dosing interval at steady-state (AUC(0-6)) were assessed by linear regression analyses. The predictive performance of single-point sampling strategies was evaluated in the validation set by mean prediction error, mean absolute error, and root mean square error. Plasma concentrations in the absorption phase yielded unsatisfactory predictions of moclobemide AUC(0-6). The best estimation of AUC(0-6) was achieved from concentrations at 4 and 6 hours following dosing. As the most reliable surrogate for moclobemide systemic exposure, concentrations at 4 and 6 hours should be used instead of predose trough concentrations as an indicator of between-patient variability and a guide for dose adjustments in specific clinical situations.
PB  - Wiley, Hoboken
T2  - Journal of Clinical Pharmacology
T1  - Evaluation of Single-Point Sampling Strategies for the Estimation of Moclobemide Exposure in Depressive Patients
VL  - 51
IS  - 5
SP  - 661
EP  - 671
DO  - 10.1177/0091270010372105
ER  - 

@article{
author = "Rakić-Ignjatović, Anita and Miljković, Branislava and Todorović, Dejan and Timotijević, Ivana and Pokrajac, Milena",
year = "2011",
abstract = "Because moclobemide pharmacokinetics vary considerably among individuals, monitoring of plasma concentrations lends insight into its pharmacokinetic behavior and enhances its rational use in clinical practice. The aim of this study was to evaluate whether single concentration-time points could adequately predict moclobemide systemic exposure. Pharmacokinetic data (full 7-point pharmacokinetic profiles), obtained from 21 depressive inpatients receiving moclobemide (150 mg 3 times daily), were randomly split into development (n = 18) and validation (n = 16) sets. Correlations between the single concentration-time points and the area under the concentration-time curve within a 6-hour dosing interval at steady-state (AUC(0-6)) were assessed by linear regression analyses. The predictive performance of single-point sampling strategies was evaluated in the validation set by mean prediction error, mean absolute error, and root mean square error. Plasma concentrations in the absorption phase yielded unsatisfactory predictions of moclobemide AUC(0-6). The best estimation of AUC(0-6) was achieved from concentrations at 4 and 6 hours following dosing. As the most reliable surrogate for moclobemide systemic exposure, concentrations at 4 and 6 hours should be used instead of predose trough concentrations as an indicator of between-patient variability and a guide for dose adjustments in specific clinical situations.",
publisher = "Wiley, Hoboken",
journal = "Journal of Clinical Pharmacology",
title = "Evaluation of Single-Point Sampling Strategies for the Estimation of Moclobemide Exposure in Depressive Patients",
volume = "51",
number = "5",
pages = "661-671",
doi = "10.1177/0091270010372105"
}

Rakić-Ignjatović, A., Miljković, B., Todorović, D., Timotijević, I.,& Pokrajac, M.. (2011). Evaluation of Single-Point Sampling Strategies for the Estimation of Moclobemide Exposure in Depressive Patients. in Journal of Clinical Pharmacology
Wiley, Hoboken., 51(5), 661-671.
https://doi.org/10.1177/0091270010372105

Rakić-Ignjatović A, Miljković B, Todorović D, Timotijević I, Pokrajac M. Evaluation of Single-Point Sampling Strategies for the Estimation of Moclobemide Exposure in Depressive Patients. in Journal of Clinical Pharmacology. 2011;51(5):661-671.
doi:10.1177/0091270010372105 .

Rakić-Ignjatović, Anita, Miljković, Branislava, Todorović, Dejan, Timotijević, Ivana, Pokrajac, Milena, "Evaluation of Single-Point Sampling Strategies for the Estimation of Moclobemide Exposure in Depressive Patients" in Journal of Clinical Pharmacology, 51, no. 5 (2011):661-671,
https://doi.org/10.1177/0091270010372105 . .

TY  - JOUR
AU  - Perović, Bojana
AU  - Jovanović, Marija
AU  - Miljković, Branislava
AU  - Vezmar, Sandra
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1392
AB  - Major depressive disorder (MDD) is a common and serious illness of our times, associated with monoamine deficiency in the brain. Moreover, increased levels of cortisol, possibly caused by stress, may be related to depression. In the treatment of MDD, the use of older antidepressants such as monoamine oxidase inhibitors and tricyclic antidepressants is decreasing rapidly, mainly due to their adverse effect profiles. In contrast, the use of serotonin reuptake inhibitors and newer antidepressants, which have dual modes of action such as inhibition of the serotonin and noradrenaline or dopamine reuptake, is increasing. Novel antidepressants have additive modes of action such as agomelatine, a potent agonist of melatonin receptors. Drugs in development for treatment of MDD include triple reuptake inhibitors, dual-acting serotonin reuptake inhibitors and histamine antagonists, and many more. Newer antidepressants have similar efficacy and in general good tolerability profiles. Nevertheless, compliance with treatment for MDD is poor and may contribute to treatment failure. Despite the broad spectrum of available antidepressants, there are still at least 30% of depressive patients who do not benefit from treatment. Therefore, new approaches in drug development are necessary and, according to current research developments, the future of antidepressant treatment may be promising.
PB  - Dove Medical Press Ltd, Albany
T2  - Neuropsychiatric Disease and Treatment
T1  - Getting the balance right: Established and emerging therapies for major depressive disorders
VL  - 6
SP  - 343
EP  - 364
DO  - 10.2147/NDT.S10485
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1392
ER  - 

@article{
author = "Perović, Bojana and Jovanović, Marija and Miljković, Branislava and Vezmar, Sandra",
year = "2010",
abstract = "Major depressive disorder (MDD) is a common and serious illness of our times, associated with monoamine deficiency in the brain. Moreover, increased levels of cortisol, possibly caused by stress, may be related to depression. In the treatment of MDD, the use of older antidepressants such as monoamine oxidase inhibitors and tricyclic antidepressants is decreasing rapidly, mainly due to their adverse effect profiles. In contrast, the use of serotonin reuptake inhibitors and newer antidepressants, which have dual modes of action such as inhibition of the serotonin and noradrenaline or dopamine reuptake, is increasing. Novel antidepressants have additive modes of action such as agomelatine, a potent agonist of melatonin receptors. Drugs in development for treatment of MDD include triple reuptake inhibitors, dual-acting serotonin reuptake inhibitors and histamine antagonists, and many more. Newer antidepressants have similar efficacy and in general good tolerability profiles. Nevertheless, compliance with treatment for MDD is poor and may contribute to treatment failure. Despite the broad spectrum of available antidepressants, there are still at least 30% of depressive patients who do not benefit from treatment. Therefore, new approaches in drug development are necessary and, according to current research developments, the future of antidepressant treatment may be promising.",
publisher = "Dove Medical Press Ltd, Albany",
journal = "Neuropsychiatric Disease and Treatment",
title = "Getting the balance right: Established and emerging therapies for major depressive disorders",
volume = "6",
pages = "343-364",
doi = "10.2147/NDT.S10485",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1392"
}

Perović, B., Jovanović, M., Miljković, B.,& Vezmar, S.. (2010). Getting the balance right: Established and emerging therapies for major depressive disorders. in Neuropsychiatric Disease and Treatment
Dove Medical Press Ltd, Albany., 6, 343-364.
https://doi.org/10.2147/NDT.S10485
https://hdl.handle.net/21.15107/rcub_farfar_1392

Perović B, Jovanović M, Miljković B, Vezmar S. Getting the balance right: Established and emerging therapies for major depressive disorders. in Neuropsychiatric Disease and Treatment. 2010;6:343-364.
doi:10.2147/NDT.S10485
https://hdl.handle.net/21.15107/rcub_farfar_1392 .

Perović, Bojana, Jovanović, Marija, Miljković, Branislava, Vezmar, Sandra, "Getting the balance right: Established and emerging therapies for major depressive disorders" in Neuropsychiatric Disease and Treatment, 6 (2010):343-364,
https://doi.org/10.2147/NDT.S10485 .,
https://hdl.handle.net/21.15107/rcub_farfar_1392 .

TY  - JOUR
AU  - Perić, Aneta
AU  - Toskić-Radojičić, Marija
AU  - Dobrić, Silva
AU  - Damjanov, Nemanja
AU  - Miljković, Branislava
AU  - Antunović, Mirjana
AU  - Vezmar, Sandra
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1366
AB  - Rationale In developed countries, cyclooxygenase 2 (COX-2) inhibitors were shown to be less costly than the combination of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) in treatment of patients with high risk of serious gastrointestinal (GI) adverse effects. It is questionable if such results apply to developing countries where health service costs are lower and there is high discrepancy between generic and patent protected drug prices. We analysed the direct cost of treatment with generic NSAIDs in combination with PPIs versus branded COX-2 inhibitors in patients with high risk of serious GI adverse effects from the perspective of the public health service in Serbia. Methods Total cost of treatment of serious GI complications and the use of NSAID+PPI versus COX-2 inhibitors were calculated. A model for estimation of cost of treatment of NSAID+PPI versus COX-2 inhibitors which included the probability of developing serious GI adverse effects was developed. Results Total cost of treatment of serious GI adverse effects resulted in an average of $814/patient. Considering the relative risk of such adverse effects for patients with four or more risk factors, the least costly treatment over 6 months was the use of celecoxib ($487). Compared with diclofenac+omeprazole, cost savings were estimated at $59 and $22 per patient with celecoxib and etoricoxib, respectively. Conclusion Cost savings may be achieved by using COX-2 inhibitors in patients at high risk of GI adverse effects even in countries with moderate health care service expenditures. Such possibility requires further investigation.
PB  - Wiley-Blackwell, Malden
T2  - Journal of Evaluation in Clinical Practice
T1  - Are COX-2 inhibitors preferable to combined NSAID and PPI in countries with moderate health service expenditures?
VL  - 16
IS  - 6
SP  - 1090
EP  - 1095
DO  - 10.1111/j.1365-2753.2009.01258.x
ER  - 

@article{
author = "Perić, Aneta and Toskić-Radojičić, Marija and Dobrić, Silva and Damjanov, Nemanja and Miljković, Branislava and Antunović, Mirjana and Vezmar, Sandra",
year = "2010",
abstract = "Rationale In developed countries, cyclooxygenase 2 (COX-2) inhibitors were shown to be less costly than the combination of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) in treatment of patients with high risk of serious gastrointestinal (GI) adverse effects. It is questionable if such results apply to developing countries where health service costs are lower and there is high discrepancy between generic and patent protected drug prices. We analysed the direct cost of treatment with generic NSAIDs in combination with PPIs versus branded COX-2 inhibitors in patients with high risk of serious GI adverse effects from the perspective of the public health service in Serbia. Methods Total cost of treatment of serious GI complications and the use of NSAID+PPI versus COX-2 inhibitors were calculated. A model for estimation of cost of treatment of NSAID+PPI versus COX-2 inhibitors which included the probability of developing serious GI adverse effects was developed. Results Total cost of treatment of serious GI adverse effects resulted in an average of $814/patient. Considering the relative risk of such adverse effects for patients with four or more risk factors, the least costly treatment over 6 months was the use of celecoxib ($487). Compared with diclofenac+omeprazole, cost savings were estimated at $59 and $22 per patient with celecoxib and etoricoxib, respectively. Conclusion Cost savings may be achieved by using COX-2 inhibitors in patients at high risk of GI adverse effects even in countries with moderate health care service expenditures. Such possibility requires further investigation.",
publisher = "Wiley-Blackwell, Malden",
journal = "Journal of Evaluation in Clinical Practice",
title = "Are COX-2 inhibitors preferable to combined NSAID and PPI in countries with moderate health service expenditures?",
volume = "16",
number = "6",
pages = "1090-1095",
doi = "10.1111/j.1365-2753.2009.01258.x"
}

Perić, A., Toskić-Radojičić, M., Dobrić, S., Damjanov, N., Miljković, B., Antunović, M.,& Vezmar, S.. (2010). Are COX-2 inhibitors preferable to combined NSAID and PPI in countries with moderate health service expenditures?. in Journal of Evaluation in Clinical Practice
Wiley-Blackwell, Malden., 16(6), 1090-1095.
https://doi.org/10.1111/j.1365-2753.2009.01258.x

Perić A, Toskić-Radojičić M, Dobrić S, Damjanov N, Miljković B, Antunović M, Vezmar S. Are COX-2 inhibitors preferable to combined NSAID and PPI in countries with moderate health service expenditures?. in Journal of Evaluation in Clinical Practice. 2010;16(6):1090-1095.
doi:10.1111/j.1365-2753.2009.01258.x .

Perić, Aneta, Toskić-Radojičić, Marija, Dobrić, Silva, Damjanov, Nemanja, Miljković, Branislava, Antunović, Mirjana, Vezmar, Sandra, "Are COX-2 inhibitors preferable to combined NSAID and PPI in countries with moderate health service expenditures?" in Journal of Evaluation in Clinical Practice, 16, no. 6 (2010):1090-1095,
https://doi.org/10.1111/j.1365-2753.2009.01258.x . .

TY  - JOUR
AU  - Ristić, Svetlana
AU  - Miljković, Branislava
AU  - Vezmar, Sandra
AU  - Stanojević, Dušan
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1379
AB  - Objectives To identify changes in prescribing patterns of antibiotic prophylaxis in Caesarean delivery after introduction of local clinical guidelines. To identify changes in outcomes of prescribing antibiotics following the implementation of local clinical guidelines on antibiotic prophylaxis. Setting University of Belgrade, Medical School, Clinic of Gynaecology and Obstetrics "Narodni front" Belgrade, Serbia. Method A quantitative retrospective analysis of antibiotic use before (January-June 2005), and following (January-June 2006) implementation of guidelines on antibiotic prophylaxis in two wards. Patients who underwent Caesarean section prior to (261) and following (281) introduction of local guidelines, participated in this study. Main outcome measures Drug utilization cost presented as the number of DDD/100 bed days/eur, the average duration of hospital stay, number of wound infections. Results There was a significant change in prescribing patterns of antibiotic prophylaxis in Caesarean section following introduction of local guidelines. The use of ceftriaxone, amikacin and metronidazole decreased (57.47% vs. 11.74%; 9.19% vs. 4.27%; 61.69% vs. 46.26%, respectively). On the other hand, the use of "older" antibiotics such as gentamicin, cefuroxime, cefazolin and ampicillin increased (14.56% vs. 29.18%; 9.2% vs. 17.44%; 9.58% vs. 45.2% and 0% vs. 3.9%, respectively). DDD/100 bed days/eur analysis revealed a 47% decrease of total cost for prophylactic antibiotic treatment in Caesarean section following local guideline implementation. In contrast, rate of wound infections and duration of hospital stay were not significantly different in both groups. Conclusion In an attempt to ensure cost-effective prophylactic use of antibiotics in Caesarean delivery, local clinical guidelines were introduced. They resulted in changes in prescribing patterns of antibiotics. There was a significant decrease in use of 'third' generation of cephalosporin's whereas the use of "older" antibiotics with proven efficacy and safety increased. In contrast, there was no significant change in treatment outcomes such as wound infection and average hospital stay.
PB  - Springer, Dordrecht
T2  - Pharmacy World & Science
T1  - Are local clinical guidelines useful in promoting rational use of antibiotic prophylaxis in Caesarean delivery?
VL  - 32
IS  - 2
SP  - 139
EP  - 145
DO  - 10.1007/s11096-009-9359-z
ER  - 

@article{
author = "Ristić, Svetlana and Miljković, Branislava and Vezmar, Sandra and Stanojević, Dušan",
year = "2010",
abstract = "Objectives To identify changes in prescribing patterns of antibiotic prophylaxis in Caesarean delivery after introduction of local clinical guidelines. To identify changes in outcomes of prescribing antibiotics following the implementation of local clinical guidelines on antibiotic prophylaxis. Setting University of Belgrade, Medical School, Clinic of Gynaecology and Obstetrics "Narodni front" Belgrade, Serbia. Method A quantitative retrospective analysis of antibiotic use before (January-June 2005), and following (January-June 2006) implementation of guidelines on antibiotic prophylaxis in two wards. Patients who underwent Caesarean section prior to (261) and following (281) introduction of local guidelines, participated in this study. Main outcome measures Drug utilization cost presented as the number of DDD/100 bed days/eur, the average duration of hospital stay, number of wound infections. Results There was a significant change in prescribing patterns of antibiotic prophylaxis in Caesarean section following introduction of local guidelines. The use of ceftriaxone, amikacin and metronidazole decreased (57.47% vs. 11.74%; 9.19% vs. 4.27%; 61.69% vs. 46.26%, respectively). On the other hand, the use of "older" antibiotics such as gentamicin, cefuroxime, cefazolin and ampicillin increased (14.56% vs. 29.18%; 9.2% vs. 17.44%; 9.58% vs. 45.2% and 0% vs. 3.9%, respectively). DDD/100 bed days/eur analysis revealed a 47% decrease of total cost for prophylactic antibiotic treatment in Caesarean section following local guideline implementation. In contrast, rate of wound infections and duration of hospital stay were not significantly different in both groups. Conclusion In an attempt to ensure cost-effective prophylactic use of antibiotics in Caesarean delivery, local clinical guidelines were introduced. They resulted in changes in prescribing patterns of antibiotics. There was a significant decrease in use of 'third' generation of cephalosporin's whereas the use of "older" antibiotics with proven efficacy and safety increased. In contrast, there was no significant change in treatment outcomes such as wound infection and average hospital stay.",
publisher = "Springer, Dordrecht",
journal = "Pharmacy World & Science",
title = "Are local clinical guidelines useful in promoting rational use of antibiotic prophylaxis in Caesarean delivery?",
volume = "32",
number = "2",
pages = "139-145",
doi = "10.1007/s11096-009-9359-z"
}

Ristić, S., Miljković, B., Vezmar, S.,& Stanojević, D.. (2010). Are local clinical guidelines useful in promoting rational use of antibiotic prophylaxis in Caesarean delivery?. in Pharmacy World & Science
Springer, Dordrecht., 32(2), 139-145.
https://doi.org/10.1007/s11096-009-9359-z

Ristić S, Miljković B, Vezmar S, Stanojević D. Are local clinical guidelines useful in promoting rational use of antibiotic prophylaxis in Caesarean delivery?. in Pharmacy World & Science. 2010;32(2):139-145.
doi:10.1007/s11096-009-9359-z .

Ristić, Svetlana, Miljković, Branislava, Vezmar, Sandra, Stanojević, Dušan, "Are local clinical guidelines useful in promoting rational use of antibiotic prophylaxis in Caesarean delivery?" in Pharmacy World & Science, 32, no. 2 (2010):139-145,
https://doi.org/10.1007/s11096-009-9359-z . .

TY  - JOUR
AU  - Rakić-Ignjatović, Anita
AU  - Miljković, Branislava
AU  - Todorović, Dejan
AU  - Timotijević, Ivana
AU  - Pokrajac, Milena
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1249
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Moclobemide (MCB) undergoes extensive both presystemic and systemic metabolism that can be affected by concomitant drugs. center dot Valproic acid (VPA) and carbamazepine (CBZ) have been found to interact with psychotropic medications of all classes and many other drugs; VPA acts as a broad-spectrum inhibitor, and CBZ as a potent inducer of a variety of drug-metabolizing enzymes. center dot There have been no previous studies designed to investigate a potential pharmacokinetic (PK) interaction between MCB and VPA or CBZ; however, these agents are likely to be used concomitantly for the treatment of depressive disorders. WHAT THIS STUDY ADDS center dot VPA does not significantly affect PK or metabolism of MCB at steady state. center dot CBZ significantly decreases MCB exposure. This effect is time-dependent, being more pronounced after 3-5 weeks of co-administration. To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) on moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients. Twenty-one inpatients with recurrent endogenous depression received MCB (150 mg t.i.d.), either as monotherapy or in combination with VPA (500 mg b.i.d.) or CBZ (200 mg b.i.d.) in a nonrandomized manner. Steady-state plasma PK parameters of MCB and its two metabolites, Ro 12-8095 and Ro 12-5637, were derived. Clinical assessments of treatment efficacy were performed weekly using standard depression rating scales. CBZ, but not VPA, was associated with decreases in the MCB AUC by 35% [from 7.794 to 5.038 mg h l(-1); 95% confidence interval (CI) -4.84863, -0.66194; P = 0.01] and C-max by 28% (from 1.911 to 1.383 mg l(-1); 95% CI -0.98197, -0.07518; P  lt  0.05), and an increase in its oral clearance by 41% (from 0.323 to 0.454 l h(-1) kg(-1); 95% CI 0.00086, 0.26171; P  lt  0.05) after 4 weeks of co-administration. MCB through concentrations were also decreased, on average by 41% (from 0.950 to 0.559 mg l(-1); 95% CI -0.77479, -0.03301; P  lt  0.05). However, the efficacy in this group of patients was not inferior to the controls, for several possible reasons. Overall tolerability of all study medications was good. VPA does not significantly affect PK or metabolism of MCB, whereas CBZ time-dependently decreases MCB exposure, probably by inducing metabolism of MCB and its major plasma metabolite. The actual clinical relevance of the observed MCB-CBZ PK interaction needs to be further evaluated in a more comprehensive study.
PB  - Wiley, Hoboken
T2  - British Journal of Clinical Pharmacology
T1  - Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study
VL  - 67
IS  - 2
SP  - 199
EP  - 208
DO  - 10.1111/j.1365-2125.2008.03326.x
ER  - 

@article{
author = "Rakić-Ignjatović, Anita and Miljković, Branislava and Todorović, Dejan and Timotijević, Ivana and Pokrajac, Milena",
year = "2009",
abstract = "WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Moclobemide (MCB) undergoes extensive both presystemic and systemic metabolism that can be affected by concomitant drugs. center dot Valproic acid (VPA) and carbamazepine (CBZ) have been found to interact with psychotropic medications of all classes and many other drugs; VPA acts as a broad-spectrum inhibitor, and CBZ as a potent inducer of a variety of drug-metabolizing enzymes. center dot There have been no previous studies designed to investigate a potential pharmacokinetic (PK) interaction between MCB and VPA or CBZ; however, these agents are likely to be used concomitantly for the treatment of depressive disorders. WHAT THIS STUDY ADDS center dot VPA does not significantly affect PK or metabolism of MCB at steady state. center dot CBZ significantly decreases MCB exposure. This effect is time-dependent, being more pronounced after 3-5 weeks of co-administration. To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) on moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients. Twenty-one inpatients with recurrent endogenous depression received MCB (150 mg t.i.d.), either as monotherapy or in combination with VPA (500 mg b.i.d.) or CBZ (200 mg b.i.d.) in a nonrandomized manner. Steady-state plasma PK parameters of MCB and its two metabolites, Ro 12-8095 and Ro 12-5637, were derived. Clinical assessments of treatment efficacy were performed weekly using standard depression rating scales. CBZ, but not VPA, was associated with decreases in the MCB AUC by 35% [from 7.794 to 5.038 mg h l(-1); 95% confidence interval (CI) -4.84863, -0.66194; P = 0.01] and C-max by 28% (from 1.911 to 1.383 mg l(-1); 95% CI -0.98197, -0.07518; P  lt  0.05), and an increase in its oral clearance by 41% (from 0.323 to 0.454 l h(-1) kg(-1); 95% CI 0.00086, 0.26171; P  lt  0.05) after 4 weeks of co-administration. MCB through concentrations were also decreased, on average by 41% (from 0.950 to 0.559 mg l(-1); 95% CI -0.77479, -0.03301; P  lt  0.05). However, the efficacy in this group of patients was not inferior to the controls, for several possible reasons. Overall tolerability of all study medications was good. VPA does not significantly affect PK or metabolism of MCB, whereas CBZ time-dependently decreases MCB exposure, probably by inducing metabolism of MCB and its major plasma metabolite. The actual clinical relevance of the observed MCB-CBZ PK interaction needs to be further evaluated in a more comprehensive study.",
publisher = "Wiley, Hoboken",
journal = "British Journal of Clinical Pharmacology",
title = "Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study",
volume = "67",
number = "2",
pages = "199-208",
doi = "10.1111/j.1365-2125.2008.03326.x"
}

Rakić-Ignjatović, A., Miljković, B., Todorović, D., Timotijević, I.,& Pokrajac, M.. (2009). Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study. in British Journal of Clinical Pharmacology
Wiley, Hoboken., 67(2), 199-208.
https://doi.org/10.1111/j.1365-2125.2008.03326.x

Rakić-Ignjatović A, Miljković B, Todorović D, Timotijević I, Pokrajac M. Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study. in British Journal of Clinical Pharmacology. 2009;67(2):199-208.
doi:10.1111/j.1365-2125.2008.03326.x .

Rakić-Ignjatović, Anita, Miljković, Branislava, Todorović, Dejan, Timotijević, Ivana, Pokrajac, Milena, "Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study" in British Journal of Clinical Pharmacology, 67, no. 2 (2009):199-208,
https://doi.org/10.1111/j.1365-2125.2008.03326.x . .

TY  - JOUR
AU  - Vezmar, Sandra
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
AU  - Timotijević, Ivana
AU  - Prostran, Milica
AU  - Todorović, Zoran
AU  - Pokrajac, Milena
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1232
AB  - Although often necessary for obtaining remission following major depressive disorder, combined antidepressant treatment Is frequently associated with drug interactions and enhanced adverse drug effects. We investigated pharmacokinetic interactions following combined fluvoxamine and amitriptyline treatment and their impact on therapeutic efficacy and tolerability. Twenty-two inpatients with major depression [Hamilton Depression Scale (HAM-D) rating >= 18] were treated with either amitriptyline (75 mg/day), fluvoxamine (100 mg/day) or both. Blood samples, for determination of amitriptyline, its major metabolite nortritpyline, and fluvoxamine, were obtained after single dose administration and in steady-state. Therapeutic efficacy was evaluated using HAM-D and adverse drug effects were evaluated using the clinical global impression scale. Following combined treatment, steady-state plasma levels of nortriptyline were significantly decreased compared to monotherapy. HAM-D scores after two-week treatment showed that there was a better response to combined treatment. There was no significant difference in severity of adverse effects among groups. We observed a pharmcokinetic interaction between fluvoxamine and amitritpyline resulting in impaired metabolism of the later. However, no signifcant impact of the interaction on treatment safety was observed. Moreover, concomitant use of amitriptyline at 75mg/day and fluvoxamine at 100 mg/day was well tolerated with a more prompt and stronger onset of clinical response compared to monotherapy in patients with major depression.
PB  - Japanese Pharmacological Soc, Kyoto
T2  - Journal of Pharmacological Sciences
T1  - Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression
VL  - 110
IS  - 1
SP  - 98
EP  - 104
DO  - 10.1254/jphs.09013FP
ER  - 

@article{
author = "Vezmar, Sandra and Miljković, Branislava and Vučićević, Katarina and Timotijević, Ivana and Prostran, Milica and Todorović, Zoran and Pokrajac, Milena",
year = "2009",
abstract = "Although often necessary for obtaining remission following major depressive disorder, combined antidepressant treatment Is frequently associated with drug interactions and enhanced adverse drug effects. We investigated pharmacokinetic interactions following combined fluvoxamine and amitriptyline treatment and their impact on therapeutic efficacy and tolerability. Twenty-two inpatients with major depression [Hamilton Depression Scale (HAM-D) rating >= 18] were treated with either amitriptyline (75 mg/day), fluvoxamine (100 mg/day) or both. Blood samples, for determination of amitriptyline, its major metabolite nortritpyline, and fluvoxamine, were obtained after single dose administration and in steady-state. Therapeutic efficacy was evaluated using HAM-D and adverse drug effects were evaluated using the clinical global impression scale. Following combined treatment, steady-state plasma levels of nortriptyline were significantly decreased compared to monotherapy. HAM-D scores after two-week treatment showed that there was a better response to combined treatment. There was no significant difference in severity of adverse effects among groups. We observed a pharmcokinetic interaction between fluvoxamine and amitritpyline resulting in impaired metabolism of the later. However, no signifcant impact of the interaction on treatment safety was observed. Moreover, concomitant use of amitriptyline at 75mg/day and fluvoxamine at 100 mg/day was well tolerated with a more prompt and stronger onset of clinical response compared to monotherapy in patients with major depression.",
publisher = "Japanese Pharmacological Soc, Kyoto",
journal = "Journal of Pharmacological Sciences",
title = "Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression",
volume = "110",
number = "1",
pages = "98-104",
doi = "10.1254/jphs.09013FP"
}

Vezmar, S., Miljković, B., Vučićević, K., Timotijević, I., Prostran, M., Todorović, Z.,& Pokrajac, M.. (2009). Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression. in Journal of Pharmacological Sciences
Japanese Pharmacological Soc, Kyoto., 110(1), 98-104.
https://doi.org/10.1254/jphs.09013FP

Vezmar S, Miljković B, Vučićević K, Timotijević I, Prostran M, Todorović Z, Pokrajac M. Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression. in Journal of Pharmacological Sciences. 2009;110(1):98-104.
doi:10.1254/jphs.09013FP .

Vezmar, Sandra, Miljković, Branislava, Vučićević, Katarina, Timotijević, Ivana, Prostran, Milica, Todorović, Zoran, Pokrajac, Milena, "Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression" in Journal of Pharmacological Sciences, 110, no. 1 (2009):98-104,
https://doi.org/10.1254/jphs.09013FP . .

TY  - JOUR
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
AU  - Pokrajac, Milena
AU  - Prostran, Milica
AU  - Martinović, Žarko J.
AU  - Grabnar, Iztok
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1211
AB  - Monitoring valproic acid (VPA) concentrations is especially challenging due to its highly variable pharmacokinetics (PK) and complex interactions with other antiepileptic drugs. We used sparse routine therapeutic drug monitoring data (n = 200) from 129 adults with epilepsy to develop a population PK model of VPA, and determine the factors that influence its clearance (CL/F). Patients were on mono VPA therapy, or were concomitantly treated with carbamazepine, phenobarbital, topiramate (TPR), lamotrigine or benzodiazepines. A one-compartment model with first-order absorption and elimination was used to fit the concentration-time VPA data. Estimates generated by NONMEM indicated that VPA CL/F was influenced by the patients' body weight (increases with the 0.556 exponent), VPA daily dose (if it is greater than 1000 mg/day, CL/F increases by 43%), and co-therapy with TPR (lowering CL/F for 23%). The interindividual variability in VPA CL/F was modeled with exponentional error model. The estimated coefficient of variation was 31.9%, while the residual variability was 23.8% for the proportional and 13.2 mg/l for the additive component. The model was validated in a separate set of 24 patients, and the predictive performance was evaluated, that indicated unbias and acceptable precision. This study confirms the interaction of VPA with TPR, which is presumably dependent on VPA dose.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - The influence of drug-drug interaction and patients' characteristics on valproic acid's clearance in adults with epilepsy using nonlinear mixed effects modeling
VL  - 38
IS  - 5
SP  - 512
EP  - 518
DO  - 10.1016/j.ejps.2009.09.017
ER  - 

@article{
author = "Vučićević, Katarina and Miljković, Branislava and Pokrajac, Milena and Prostran, Milica and Martinović, Žarko J. and Grabnar, Iztok",
year = "2009",
abstract = "Monitoring valproic acid (VPA) concentrations is especially challenging due to its highly variable pharmacokinetics (PK) and complex interactions with other antiepileptic drugs. We used sparse routine therapeutic drug monitoring data (n = 200) from 129 adults with epilepsy to develop a population PK model of VPA, and determine the factors that influence its clearance (CL/F). Patients were on mono VPA therapy, or were concomitantly treated with carbamazepine, phenobarbital, topiramate (TPR), lamotrigine or benzodiazepines. A one-compartment model with first-order absorption and elimination was used to fit the concentration-time VPA data. Estimates generated by NONMEM indicated that VPA CL/F was influenced by the patients' body weight (increases with the 0.556 exponent), VPA daily dose (if it is greater than 1000 mg/day, CL/F increases by 43%), and co-therapy with TPR (lowering CL/F for 23%). The interindividual variability in VPA CL/F was modeled with exponentional error model. The estimated coefficient of variation was 31.9%, while the residual variability was 23.8% for the proportional and 13.2 mg/l for the additive component. The model was validated in a separate set of 24 patients, and the predictive performance was evaluated, that indicated unbias and acceptable precision. This study confirms the interaction of VPA with TPR, which is presumably dependent on VPA dose.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "The influence of drug-drug interaction and patients' characteristics on valproic acid's clearance in adults with epilepsy using nonlinear mixed effects modeling",
volume = "38",
number = "5",
pages = "512-518",
doi = "10.1016/j.ejps.2009.09.017"
}

Vučićević, K., Miljković, B., Pokrajac, M., Prostran, M., Martinović, Ž. J.,& Grabnar, I.. (2009). The influence of drug-drug interaction and patients' characteristics on valproic acid's clearance in adults with epilepsy using nonlinear mixed effects modeling. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 38(5), 512-518.
https://doi.org/10.1016/j.ejps.2009.09.017

Vučićević K, Miljković B, Pokrajac M, Prostran M, Martinović ŽJ, Grabnar I. The influence of drug-drug interaction and patients' characteristics on valproic acid's clearance in adults with epilepsy using nonlinear mixed effects modeling. in European Journal of Pharmaceutical Sciences. 2009;38(5):512-518.
doi:10.1016/j.ejps.2009.09.017 .

Vučićević, Katarina, Miljković, Branislava, Pokrajac, Milena, Prostran, Milica, Martinović, Žarko J., Grabnar, Iztok, "The influence of drug-drug interaction and patients' characteristics on valproic acid's clearance in adults with epilepsy using nonlinear mixed effects modeling" in European Journal of Pharmaceutical Sciences, 38, no. 5 (2009):512-518,
https://doi.org/10.1016/j.ejps.2009.09.017 . .

TY  - JOUR
AU  - Stepanović-Petrović, Radica
AU  - Tomić, Maja
AU  - Vučković, Sonja M.
AU  - Kocev, Nikola
AU  - Ugrešić, Nenad
AU  - Prostran, Milica
AU  - Bošković, Bogdan
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1092
AB  - Background/Aims: The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline ( GABA A receptor antagonist) on these effects of antiepileptic drugs. Methods: Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A ( Con A). A paw-pressure test was used to determine: ( 1) the development of hyperalgesia induced by Con A; ( 2) the effects of carbamazepine/ oxcarbazepine on Con A-induced hyperalgesia, and ( 3) the effects of bicuculline on the carbamazepine/ oxcarbazepine antihyperalgesia. Results: Intraperitoneally injected bicuculline (0.5 - 1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine ( 27 mg/ kg, i.p.) and oxcarbazepine ( 80 mg/ kg, i.p.). When applied intraplantarly, bicuculline ( 0.14 mg/ paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine ( 0.14 mg/ paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. Conclusion: These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA A receptor activation. Copyright
PB  - Karger, Basel
T2  - Pharmacology
T1  - GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia
VL  - 82
IS  - 1
SP  - 53
EP  - 58
DO  - 10.1159/000127841
ER  - 

@article{
author = "Stepanović-Petrović, Radica and Tomić, Maja and Vučković, Sonja M. and Kocev, Nikola and Ugrešić, Nenad and Prostran, Milica and Bošković, Bogdan",
year = "2008",
abstract = "Background/Aims: The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline ( GABA A receptor antagonist) on these effects of antiepileptic drugs. Methods: Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A ( Con A). A paw-pressure test was used to determine: ( 1) the development of hyperalgesia induced by Con A; ( 2) the effects of carbamazepine/ oxcarbazepine on Con A-induced hyperalgesia, and ( 3) the effects of bicuculline on the carbamazepine/ oxcarbazepine antihyperalgesia. Results: Intraperitoneally injected bicuculline (0.5 - 1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine ( 27 mg/ kg, i.p.) and oxcarbazepine ( 80 mg/ kg, i.p.). When applied intraplantarly, bicuculline ( 0.14 mg/ paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine ( 0.14 mg/ paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. Conclusion: These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA A receptor activation. Copyright",
publisher = "Karger, Basel",
journal = "Pharmacology",
title = "GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia",
volume = "82",
number = "1",
pages = "53-58",
doi = "10.1159/000127841"
}

Stepanović-Petrović, R., Tomić, M., Vučković, S. M., Kocev, N., Ugrešić, N., Prostran, M.,& Bošković, B.. (2008). GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia. in Pharmacology
Karger, Basel., 82(1), 53-58.
https://doi.org/10.1159/000127841

Stepanović-Petrović R, Tomić M, Vučković SM, Kocev N, Ugrešić N, Prostran M, Bošković B. GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia. in Pharmacology. 2008;82(1):53-58.
doi:10.1159/000127841 .

Stepanović-Petrović, Radica, Tomić, Maja, Vučković, Sonja M., Kocev, Nikola, Ugrešić, Nenad, Prostran, Milica, Bošković, Bogdan, "GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia" in Pharmacology, 82, no. 1 (2008):53-58,
https://doi.org/10.1159/000127841 . .

TY  - JOUR
AU  - Stepanović-Petrović, Radica
AU  - Tomić, Maja
AU  - Vučković, Sonja M.
AU  - Paranos, Sonja
AU  - Ugrešić, Nenad
AU  - Prostran, Milica
AU  - Milovanović, Slobocian
AU  - Bošković, Bogdan
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1067
AB  - BACKGROUND: There is evidence supporting the antinociceptive effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in various models of neuropathic pain as well as inflammatory somatic pain. Data are lacking on the antinociceptive potential of these drugs against visceral pain. In this study, we examined and compared the effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in the writhing test as a visceral pain model in the mouse. In addition, the influence of these anticonvulsants on motor performance was examined to compare the tolerability of these anticonvulsants when used against acute visceral pain. METHODS: The antinociceptive effects of these anticonvulsants were examined in the acetic acid writhing test in mice. The side effect propensity of these drugs was examined using the rotarod test. RESULTS: Carbamazepine (25-60 mg/kg; p.o.), oxcarbazepine (10-40 mg/kg; p.o.), gabapentin (10-70 mg/kg; p.o.), and topiramate (5-30 mg/kg; p.o.) caused a significant dose-dependent reduction the number of writhes in the writhing test. In the rotarod test, carbamazepine (60-140 mg/kg; p.o.) and oxcarbazepine (120-450 mg/kg; p.o.) significantly reduced the time spent on the rotarod in a dose- and time-dependent manner. Gabapentin (1000-2000 mg/kg; p.o.) and topiramate (400-1500 mg/kg; p.o.) did not produce significant impairment of motor performance at the highest doses used. The therapeutic index (motor impairing dose TD50)/writhing ED50) values were topiramate (>148.5) > gabapentin (>60.2) > oxcarbazepine (15.2) > carbamazepine (2.3). CONCLUSIONS: These results indicate that oxcarbazepine, gabapentin, and topiramate are effective in the writhing model in mice, in a dose range, which is not related to motor impairment; topiramate is the most potent and the most tolerable drug.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Anesthesia and Analgesia
T1  - The antinociceptive effects of anticonvulsants in a mouse visceral pain model
VL  - 106
IS  - 6
SP  - 1897
EP  - 1903
DO  - 10.1213/ane.0b013618172b993
ER  - 

@article{
author = "Stepanović-Petrović, Radica and Tomić, Maja and Vučković, Sonja M. and Paranos, Sonja and Ugrešić, Nenad and Prostran, Milica and Milovanović, Slobocian and Bošković, Bogdan",
year = "2008",
abstract = "BACKGROUND: There is evidence supporting the antinociceptive effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in various models of neuropathic pain as well as inflammatory somatic pain. Data are lacking on the antinociceptive potential of these drugs against visceral pain. In this study, we examined and compared the effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in the writhing test as a visceral pain model in the mouse. In addition, the influence of these anticonvulsants on motor performance was examined to compare the tolerability of these anticonvulsants when used against acute visceral pain. METHODS: The antinociceptive effects of these anticonvulsants were examined in the acetic acid writhing test in mice. The side effect propensity of these drugs was examined using the rotarod test. RESULTS: Carbamazepine (25-60 mg/kg; p.o.), oxcarbazepine (10-40 mg/kg; p.o.), gabapentin (10-70 mg/kg; p.o.), and topiramate (5-30 mg/kg; p.o.) caused a significant dose-dependent reduction the number of writhes in the writhing test. In the rotarod test, carbamazepine (60-140 mg/kg; p.o.) and oxcarbazepine (120-450 mg/kg; p.o.) significantly reduced the time spent on the rotarod in a dose- and time-dependent manner. Gabapentin (1000-2000 mg/kg; p.o.) and topiramate (400-1500 mg/kg; p.o.) did not produce significant impairment of motor performance at the highest doses used. The therapeutic index (motor impairing dose TD50)/writhing ED50) values were topiramate (>148.5) > gabapentin (>60.2) > oxcarbazepine (15.2) > carbamazepine (2.3). CONCLUSIONS: These results indicate that oxcarbazepine, gabapentin, and topiramate are effective in the writhing model in mice, in a dose range, which is not related to motor impairment; topiramate is the most potent and the most tolerable drug.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Anesthesia and Analgesia",
title = "The antinociceptive effects of anticonvulsants in a mouse visceral pain model",
volume = "106",
number = "6",
pages = "1897-1903",
doi = "10.1213/ane.0b013618172b993"
}

Stepanović-Petrović, R., Tomić, M., Vučković, S. M., Paranos, S., Ugrešić, N., Prostran, M., Milovanović, S.,& Bošković, B.. (2008). The antinociceptive effects of anticonvulsants in a mouse visceral pain model. in Anesthesia and Analgesia
Lippincott Williams & Wilkins, Philadelphia., 106(6), 1897-1903.
https://doi.org/10.1213/ane.0b013618172b993

Stepanović-Petrović R, Tomić M, Vučković SM, Paranos S, Ugrešić N, Prostran M, Milovanović S, Bošković B. The antinociceptive effects of anticonvulsants in a mouse visceral pain model. in Anesthesia and Analgesia. 2008;106(6):1897-1903.
doi:10.1213/ane.0b013618172b993 .

Stepanović-Petrović, Radica, Tomić, Maja, Vučković, Sonja M., Paranos, Sonja, Ugrešić, Nenad, Prostran, Milica, Milovanović, Slobocian, Bošković, Bogdan, "The antinociceptive effects of anticonvulsants in a mouse visceral pain model" in Anesthesia and Analgesia, 106, no. 6 (2008):1897-1903,
https://doi.org/10.1213/ane.0b013618172b993 . .

TY  - JOUR
AU  - Tomić, Maja
AU  - Vučković, Sonja M.
AU  - Stepanović-Petrović, Radica
AU  - Ugrešić, Nenad
AU  - Paranos, Sonja
AU  - Prostran, Milica
AU  - Bošković, Bogdan
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/983
AB  - We studied whether peripheral alpha(2)-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha(2)-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)- adrenoceptor antagonist), MK-912 (selective alpha(2C)-adrenoceptor antagonist), and clonidine (alpha(2)-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. METHODS: Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia. RESULTS: Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.. pl.), BRL44408 (100 and 200 nmol/paw,-i.pl.),and MK-912 (10and 20 nmol/paw;i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/pav\T,I i.pl.) in a close-dependent mariner. The effects of antagonists were due to local effects since they were not observed after admirdstration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED50 (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. lsobolographic analysis revealed an additive antihyperalgesic effect. CONCLUSIONS: Our results indicate that the peripheral a,A and a,c adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia. (Anesth Analg 2007;105:1474-81)
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Anesthesia and Analgesia
T1  - The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain
VL  - 105
IS  - 5
SP  - 1474
EP  - 1481
DO  - 10.1213/01.ane.0000287270.35176.3e
ER  - 

@article{
author = "Tomić, Maja and Vučković, Sonja M. and Stepanović-Petrović, Radica and Ugrešić, Nenad and Paranos, Sonja and Prostran, Milica and Bošković, Bogdan",
year = "2007",
abstract = "We studied whether peripheral alpha(2)-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha(2)-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)- adrenoceptor antagonist), MK-912 (selective alpha(2C)-adrenoceptor antagonist), and clonidine (alpha(2)-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. METHODS: Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia. RESULTS: Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.. pl.), BRL44408 (100 and 200 nmol/paw,-i.pl.),and MK-912 (10and 20 nmol/paw;i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/pav\T,I i.pl.) in a close-dependent mariner. The effects of antagonists were due to local effects since they were not observed after admirdstration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED50 (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. lsobolographic analysis revealed an additive antihyperalgesic effect. CONCLUSIONS: Our results indicate that the peripheral a,A and a,c adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia. (Anesth Analg 2007;105:1474-81)",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Anesthesia and Analgesia",
title = "The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain",
volume = "105",
number = "5",
pages = "1474-1481",
doi = "10.1213/01.ane.0000287270.35176.3e"
}

Tomić, M., Vučković, S. M., Stepanović-Petrović, R., Ugrešić, N., Paranos, S., Prostran, M.,& Bošković, B.. (2007). The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain. in Anesthesia and Analgesia
Lippincott Williams & Wilkins, Philadelphia., 105(5), 1474-1481.
https://doi.org/10.1213/01.ane.0000287270.35176.3e

Tomić M, Vučković SM, Stepanović-Petrović R, Ugrešić N, Paranos S, Prostran M, Bošković B. The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain. in Anesthesia and Analgesia. 2007;105(5):1474-1481.
doi:10.1213/01.ane.0000287270.35176.3e .

Tomić, Maja, Vučković, Sonja M., Stepanović-Petrović, Radica, Ugrešić, Nenad, Paranos, Sonja, Prostran, Milica, Bošković, Bogdan, "The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain" in Anesthesia and Analgesia, 105, no. 5 (2007):1474-1481,
https://doi.org/10.1213/01.ane.0000287270.35176.3e . .