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Katarina Vučićević
Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy-University of Belgrade, Vojvode Stepe 450, Belgrade 11221, Republic of Serbia

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Journal article
Published: 25 February 2020 in European Journal of Pharmaceutical Sciences
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The release and absorption profile of an oral medication is influenced by the physicochemical properties of the drug and its formulation, as well as by the anatomy and physiology of the gastrointestinal (GI) tract. During drug development the bioavailability of a new drug is typically assessed in early clinical studies in a healthy adult population. However, many disease conditions are associated with an alteration of the anatomy and/or physiology of the GI tract. The same holds true for some subpopulations, such as paediatric or elderly patients, or populations with different ethnicity. The variation in GI tract conditions compared to healthy adults can directly affect the kinetics of drug absorption, and thus, safety and efficacy of an oral medication. This review provides an overview of GI tract properties in special populations compared to healthy adults and discusses how drug absorption is affected by these conditions. Particular focus is directed towards non-disease dependent conditions (age, sex, ethnicity, genetic factors, obesity, pregnancy), GI diseases (ulcerative colitis and Crohn's disease, celiac disease, cancer in the GI tract, Roux-en-Y gastric bypass, lactose intolerance, Helicobacter pylori infection, and infectious diseases of the GI tract), as well as systemic diseases that change the GI tract conditions (cystic fibrosis, diabetes, Parkinson's disease, HIV enteropathy, and critical illness). The current knowledge about GI conditions in special populations and their impact on drug absorption is still limited. Further research is required to improve confidence in pharmacokinetic predictions and dosing recommendations in the targeted patient population, and thus to ensure safe and effective drug therapies.

ACS Style

Cordula Stillhart; Katarina Vučićević; Patrick Augustijns; Abdul W. Basit; Hannah Batchelor; Talia R. Flanagan; Ina Gesquiere; Rick Greupink; Daniel Keszthelyi; Mikko Koskinen; Christine M. Madla; Christophe Matthys; Goran Miljuš; Miriam G. Mooij; Neil Parrott; Anna-Lena Ungell; Saskia N. de Wildt; Mine Orlu; Sandra Klein; Anette Müllertz. Impact of gastrointestinal physiology on drug absorption in special populations––An UNGAP review. European Journal of Pharmaceutical Sciences 2020, 147, 105280 .

AMA Style

Cordula Stillhart, Katarina Vučićević, Patrick Augustijns, Abdul W. Basit, Hannah Batchelor, Talia R. Flanagan, Ina Gesquiere, Rick Greupink, Daniel Keszthelyi, Mikko Koskinen, Christine M. Madla, Christophe Matthys, Goran Miljuš, Miriam G. Mooij, Neil Parrott, Anna-Lena Ungell, Saskia N. de Wildt, Mine Orlu, Sandra Klein, Anette Müllertz. Impact of gastrointestinal physiology on drug absorption in special populations––An UNGAP review. European Journal of Pharmaceutical Sciences. 2020; 147 ():105280.

Chicago/Turabian Style

Cordula Stillhart; Katarina Vučićević; Patrick Augustijns; Abdul W. Basit; Hannah Batchelor; Talia R. Flanagan; Ina Gesquiere; Rick Greupink; Daniel Keszthelyi; Mikko Koskinen; Christine M. Madla; Christophe Matthys; Goran Miljuš; Miriam G. Mooij; Neil Parrott; Anna-Lena Ungell; Saskia N. de Wildt; Mine Orlu; Sandra Klein; Anette Müllertz. 2020. "Impact of gastrointestinal physiology on drug absorption in special populations––An UNGAP review." European Journal of Pharmaceutical Sciences 147, no. : 105280.

Review article
Published: 02 January 2020 in Drug Metabolism Reviews
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Antipsychotic medicines are widely used for the management of psychotic symptoms regardless of the underlying diagnosis. Most atypical antipsychotics undergo extensive metabolism prior to excretion. Various factors may influence their pharmacokinetics, particularly elimination, leading to highly variable drug concentrations between individual patients following the same dosing regimen. Population pharmacokinetic approach, based on nonlinear mixed effects modeling, is a useful tool to identify covariates explaining pharmacokinetic variability, as well as to characterize and distinguish unexplained residual and between-subject (interindividual) variability. In addition, this approach allows the use of both sparsely and intensively sampled data. In this paper, we reviewed the pharmacokinetic characteristics of clozapine, olanzapine and aripiprazole, focusing on a population modeling approach. In particular, models based on a nonlinear mixed effects approach performed by NONMEM® software in order to identify and quantify sources of pharmacokinetic variability are presented. Population models were identified through systematic searches of PubMed and sixteen studies were selected. Some of the factors identified that significantly contribute to variability in elimination among clozapine, olanzapine, and aripiprazole are demographic characteristics, body weight, genetic polymorphism, smoking and in some cases drug interactions. Scientific research based on pharmacometric modeling is useful to further characterize sources of variability and their combined effect.

ACS Style

Marija Jovanović; Katarina Vučićević; Branislava Miljković. Understanding variability in the pharmacokinetics of atypical antipsychotics – focus on clozapine, olanzapine and aripiprazole population models. Drug Metabolism Reviews 2020, 52, 1 -18.

AMA Style

Marija Jovanović, Katarina Vučićević, Branislava Miljković. Understanding variability in the pharmacokinetics of atypical antipsychotics – focus on clozapine, olanzapine and aripiprazole population models. Drug Metabolism Reviews. 2020; 52 (1):1-18.

Chicago/Turabian Style

Marija Jovanović; Katarina Vučićević; Branislava Miljković. 2020. "Understanding variability in the pharmacokinetics of atypical antipsychotics – focus on clozapine, olanzapine and aripiprazole population models." Drug Metabolism Reviews 52, no. 1: 1-18.

Journal article
Published: 01 January 2020 in Arhiv za farmaciju
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High dose methotrexate (MTX) is used in therapy of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients. It acts as competitive inhibitor of dihydrofolate reductase and consequently inhibits synthesis of deoxyribonucleic acid. The bioavailability is dependent upon dose and route of administration. The drug is moderately bound to plasma proteins and distributes in body tissues and cells. After the administration in high doses, MTX partially undergoes hepatic and intracellular metabolism, but renal excretion of parent compound is the main route of elimination. Numerous factors may influence pharmacokinetics and concentration of drug, but primarily the effect of renal function on elimination is described. Delayed elimination might also be the consequence of drug interaction in renal tubules. Toxicity can arise with high MTX doses, especially in patients with delayed MTX elimination. Therapeutic drug monitoring is indicated due to safety reasons, in order to optimize leucovorin (folinic acid) administration as it reduces MTX toxicity. Considering the variability and the toxicity of high dose MTX therapy, special caution is required in pediatric patients.

ACS Style

Biljana Škorić; Marija Jovanović; Branislava Miljković; Miloš Kuzmanović; Katarina Vučićević. Clinical pharmacokinetics of methotrexate in the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients. Arhiv za farmaciju 2020, 70, 20 -33.

AMA Style

Biljana Škorić, Marija Jovanović, Branislava Miljković, Miloš Kuzmanović, Katarina Vučićević. Clinical pharmacokinetics of methotrexate in the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients. Arhiv za farmaciju. 2020; 70 (1):20-33.

Chicago/Turabian Style

Biljana Škorić; Marija Jovanović; Branislava Miljković; Miloš Kuzmanović; Katarina Vučićević. 2020. "Clinical pharmacokinetics of methotrexate in the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients." Arhiv za farmaciju 70, no. 1: 20-33.

Journal article
Published: 05 November 2019 in Journal of Critical Care
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The present study aimed to establish a population pharmacokinetic model of vancomycin, including adult critically ill septic patients, with normal and impaired renal function. A prospective analysis of 146 concentrations from 73 adult critically ill septic patients treated with 1-h intravenous infusion of vancomycin were included in the study. A nonlinear mixed effects modeling (NONMEM) approach was applied for data analysis and evaluation of the final model. The influence of creatinine clearance calculated by the Cockcroft-Gault equation (CrCl), and other potential covariates on vancomycin clearance (CL) were evaluated. The final one-compartment pharmacokinetic model includes the effect of CrCl on CL. Population pharmacokinetic values for a typical subject were estimated at 0.024 l/h for CL dependent on renal function (CLCrCl), 1.93 l/h for residual portion of CL (not dependent on renal function), and 0.511 l/kg for volume of distribution (V). According to the final model, for patients with CrCl = 120 ml/min, the median vancomycin total CL is 4.81 l/h, while CrCl-dependent fraction accounts for approximately 60% of CL. The developed population vancomycin model may be used in estimating individual CL for adult critically ill septic patients, and could be applied for individualizing dosage regimens taking into account the continuous effect of CrCl.

ACS Style

Tijana Kovacevic; Branislava Miljkovic; Pedja Kovacevic; Sasa Dragic; Danica Momcicevic; Sanja Avram; Marija Jovanovic; Katarina Vucicevic. Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients. Journal of Critical Care 2019, 55, 116 -121.

AMA Style

Tijana Kovacevic, Branislava Miljkovic, Pedja Kovacevic, Sasa Dragic, Danica Momcicevic, Sanja Avram, Marija Jovanovic, Katarina Vucicevic. Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients. Journal of Critical Care. 2019; 55 ():116-121.

Chicago/Turabian Style

Tijana Kovacevic; Branislava Miljkovic; Pedja Kovacevic; Sasa Dragic; Danica Momcicevic; Sanja Avram; Marija Jovanovic; Katarina Vucicevic. 2019. "Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients." Journal of Critical Care 55, no. : 116-121.

Journal article
Published: 23 July 2019 in Toxins
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The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival.

ACS Style

Djurdja Jerotic; Marija Matic; Sonja Suvakov; Katarina Vucicevic; Tatjana Damjanovic; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Vesna Coric; Aleksandra Stefanovic; Jasmina Ivanisevic; Zorana Jelic-Ivanovic; Lana McClements; Nada Dimkovic; Tatjana Simic. Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients. Toxins 2019, 11, 431 .

AMA Style

Djurdja Jerotic, Marija Matic, Sonja Suvakov, Katarina Vucicevic, Tatjana Damjanovic, Ana Savic-Radojevic, Marija Pljesa-Ercegovac, Vesna Coric, Aleksandra Stefanovic, Jasmina Ivanisevic, Zorana Jelic-Ivanovic, Lana McClements, Nada Dimkovic, Tatjana Simic. Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients. Toxins. 2019; 11 (7):431.

Chicago/Turabian Style

Djurdja Jerotic; Marija Matic; Sonja Suvakov; Katarina Vucicevic; Tatjana Damjanovic; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Vesna Coric; Aleksandra Stefanovic; Jasmina Ivanisevic; Zorana Jelic-Ivanovic; Lana McClements; Nada Dimkovic; Tatjana Simic. 2019. "Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients." Toxins 11, no. 7: 431.

Original article
Published: 29 May 2019 in British Journal of Clinical Pharmacology
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Aims Generic products can be regarded as therapeutically equivalent and switchable with the reference product. However, switchability between generics is unknown, as direct comparisons between generics are not performed. The aim of this study was to investigate the bioequivalence between generic clopidogrel products by means of adjusted indirect comparisons (AICs). Methods AICs were conducted to assess bioequivalence between 4 generic clopidogrel products that are authorised in Serbia. Generics are considered equivalent to the reference if the 90% confidence intervals (CIs) for the ratios test/reference of the maximum concentration (Cmax) and area under the curve up to the last measurable concentration (AUC0–t) fall within the acceptance range 80.00–125.00%. However, for AICs between generics, the Canadian acceptance criterion for Cmax was employed, where only the point estimate of Cmax needs to be within 80.00–125.00%. Results The 90% CIs of the AICs demonstrated bioequivalence within 80.00–125.00% for all AUC0–t comparisons. The point estimates of Cmax in all AICs were also within this range. Conclusion This study demonstrates that the bioavailability of these 4 generic clopidogrel products authorised in Serbia is very similar. Despite the limited power of AICs, bioequivalence was demonstrated for all 90% CIs of AUC0–t and all 90% CIs of Cmax comparisons were within or very close to the acceptance range, being able to comply with the acceptance criterion employed in Canada for Cmax. Therefore, these 4 generic clopidogrel products authorised in Serbia can be considered switchable with each other in clinical practice based on the adjusted indirect comparisons.

ACS Style

Zorica Pejčić; Katarina Vučićević; Alfredo García‐Arieta; Branislava Miljković. Adjusted indirect comparisons to assess bioequivalence between generic clopidogrel products in Serbia. British Journal of Clinical Pharmacology 2019, 85, 2059 -2065.

AMA Style

Zorica Pejčić, Katarina Vučićević, Alfredo García‐Arieta, Branislava Miljković. Adjusted indirect comparisons to assess bioequivalence between generic clopidogrel products in Serbia. British Journal of Clinical Pharmacology. 2019; 85 (9):2059-2065.

Chicago/Turabian Style

Zorica Pejčić; Katarina Vučićević; Alfredo García‐Arieta; Branislava Miljković. 2019. "Adjusted indirect comparisons to assess bioequivalence between generic clopidogrel products in Serbia." British Journal of Clinical Pharmacology 85, no. 9: 2059-2065.

Journal article
Published: 01 January 2019 in Arhiv za farmaciju
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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. klinički značajne interakcije; opioidni i neopioidni analgetici; mehanizam interakcija; farmaceut

ACS Style

Sandra Vezmar-Kovačević; Katarina Vučićević; Valentina Topić-Vučenović; Zvezdana Rajkovača; Branislava Miljković. Clinically important drug interactions with opioid and non-opioid analgesics. Arhiv za farmaciju 2019, 69, 1071 -1083.

AMA Style

Sandra Vezmar-Kovačević, Katarina Vučićević, Valentina Topić-Vučenović, Zvezdana Rajkovača, Branislava Miljković. Clinically important drug interactions with opioid and non-opioid analgesics. Arhiv za farmaciju. 2019; 69 (1):1071-1083.

Chicago/Turabian Style

Sandra Vezmar-Kovačević; Katarina Vučićević; Valentina Topić-Vučenović; Zvezdana Rajkovača; Branislava Miljković. 2019. "Clinically important drug interactions with opioid and non-opioid analgesics." Arhiv za farmaciju 69, no. 1: 1071-1083.

Clinical study
Published: 01 June 2018 in Research in Social and Administrative Pharmacy
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Asthma self-management is aimed to improve the quality and effectiveness of asthma care by supporting the patients to manage their illness by themselves.The aim of the study was to evaluate the impact of pharmacist-delivered counselling on patients knowledge and beliefs about the medicines, adherence level, and asthma control.A prospective intervention study was conducted in community pharmacies. A total of 90 patients completed the study. Four questionnaires were used: (1) Beliefs about medicines questionnaire (BMQ), (2) Knowledge of asthma and asthma medicine (KAM), (3) Asthma control test (ACT), and (4) 8-item Morisky medication adherence scale questionnaire (MMAS-8). Questionnaires were completed at baseline and 3 months later.Low level of adherence and poor asthma control were determined initially. Better asthma control was significantly associated with higher adherence level, lower concerns regarding the medication use, and knowledge of triggers. Statistically significant improvement was found after 3 months in patients knowledge of asthma and its medications, their attitude towards medications (decrease in harm, overuse and concern; increase in necessity score), asthma control score (increased from 19 to 20, p < 0.05) and level of adherence (MMAS-8 score decreased from 3 to 2 p < 0.05). Better asthma control was achieved in 60% of patients. Sixteen patients (18%) were transferred from poor to well-controlled asthma, implying no need for patients' referral to the doctor and no additional cost for the health system.Improved disease control could be a result of enhanced knowledge and understanding of the disease-medication relationship, improved inhalation technique, and support on patients' adherence. Acquired knowledge and skills, as well as improved attitude, empowered patients to take a more active part in asthma management. Education in further patients' follow-up should consider topics tailored to the patients' characteristics, needs, and prior counselling schedule with issues discussed.

ACS Style

Milena Kovačević; Milica Ćulafić; Marija Jovanović; Katarina Vučićević; Sandra Vezmar Kovačević; Branislava Miljković. Impact of community pharmacists' interventions on asthma self-management care. Research in Social and Administrative Pharmacy 2018, 14, 603 -611.

AMA Style

Milena Kovačević, Milica Ćulafić, Marija Jovanović, Katarina Vučićević, Sandra Vezmar Kovačević, Branislava Miljković. Impact of community pharmacists' interventions on asthma self-management care. Research in Social and Administrative Pharmacy. 2018; 14 (6):603-611.

Chicago/Turabian Style

Milena Kovačević; Milica Ćulafić; Marija Jovanović; Katarina Vučićević; Sandra Vezmar Kovačević; Branislava Miljković. 2018. "Impact of community pharmacists' interventions on asthma self-management care." Research in Social and Administrative Pharmacy 14, no. 6: 603-611.

Pharmacokinetics and disposition
Published: 13 May 2018 in European Journal of Clinical Pharmacology
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Radioiodine (131I) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize 131I biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients’ demographic and clinical characteristics on intra-thyroidal 131I 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 131I 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 131I into the thyroid (ktu) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT4), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of 131I 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 ktu from 91 (3.9) to 53.9 (4.5)%. This is the first population model that accounts for the influence of fT4 and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to 131I and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.

ACS Style

Valentina Topić Vučenović; Zvezdana Rajkovača; Dijana Jelić; Dragi Stanimirović; Goran Vuleta; Branislava Miljković; Katarina Vučićević. Investigation of factors influencing radioiodine (131I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach. European Journal of Clinical Pharmacology 2018, 74, 1037 -1045.

AMA Style

Valentina Topić Vučenović, Zvezdana Rajkovača, Dijana Jelić, Dragi Stanimirović, Goran Vuleta, Branislava Miljković, Katarina Vučićević. Investigation of factors influencing radioiodine (131I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach. European Journal of Clinical Pharmacology. 2018; 74 (8):1037-1045.

Chicago/Turabian Style

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

Journal article
Published: 01 January 2018 in Arhiv za farmaciju
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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. klinički značajne interakcije; opioidni i neopioidni analgetici; mehanizam interakcija; farmaceut

ACS Style

Kovačević Sandra Vezmar; Katarina Vučićević; Topić Valentina Vučenović; Zvezdana Rajkovača; Branislava Miljković. Clinically important drug interactions with opioid and non-opioid analgesics. Arhiv za farmaciju 2018, 68, 1071 -1083.

AMA Style

Kovačević Sandra Vezmar, Katarina Vučićević, Topić Valentina Vučenović, Zvezdana Rajkovača, Branislava Miljković. Clinically important drug interactions with opioid and non-opioid analgesics. Arhiv za farmaciju. 2018; 68 (6):1071-1083.

Chicago/Turabian Style

Kovačević Sandra Vezmar; Katarina Vučićević; Topić Valentina Vučenović; Zvezdana Rajkovača; Branislava Miljković. 2018. "Clinically important drug interactions with opioid and non-opioid analgesics." Arhiv za farmaciju 68, no. 6: 1071-1083.

Journal article
Published: 19 December 2017 in Journal of Infectious Diseases
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A monthly treatment course of dihydroartemisinin-piperaquine (DHA-PQ) effectively prevents malaria during pregnancy. However, a drug–drug interaction pharmacokinetic (PK) study found that pregnant human immunodeficiency virus (HIV)–infected women receiving efavirenz-based antiretroviral therapy (ART) had markedly reduced piperaquine (PQ) exposure. This suggests the need for alternative DHA-PQ chemoprevention regimens in this population. Eighty-three HIV-infected pregnant women who received monthly DHA-PQ and efavirenz contributed longitudinal PK and corrected QT interval (QTc) (n = 25) data. Population PK and PK-QTc models for PQ were developed to consider the benefits (protective PQ coverage) and risks (QTc prolongation) of alternative DHA-PQ chemoprevention regimens. Protective PQ coverage was defined as maintaining a concentration >10 ng/mL for >95% of the chemoprevention period. PQ clearance was 4540 L/day. With monthly DHA-PQ (2880 mg PQ), 96% of women, respectively. All regimens were safe, with ≤2% of women predicted to have ≥30 msec QTc increase. For HIV-infected pregnant women receiving efavirenz, low daily DHA-PQ dosing was predicted to improve protection against parasitemia and reduce risk of toxicity compared to monthly dosing. NCT02282293.

ACS Style

Erika Wallender; Katarina Vučićević; Prasanna Jagannathan; Liusheng Huang; Paul Natureeba; Abel Kakuru; Mary Muhindo; Mirium Nakalembe; Diane Havlir; Moses Kamya; Francesca Aweeka; Grant Dorsey; Philip J Rosenthal; Radojka M Savic. Predicting Optimal Dihydroartemisinin-Piperaquine Regimens to Prevent Malaria During Pregnancy for Human Immunodeficiency Virus–Infected Women Receiving Efavirenz. Journal of Infectious Diseases 2017, 217, 964 -972.

AMA Style

Erika Wallender, Katarina Vučićević, Prasanna Jagannathan, Liusheng Huang, Paul Natureeba, Abel Kakuru, Mary Muhindo, Mirium Nakalembe, Diane Havlir, Moses Kamya, Francesca Aweeka, Grant Dorsey, Philip J Rosenthal, Radojka M Savic. Predicting Optimal Dihydroartemisinin-Piperaquine Regimens to Prevent Malaria During Pregnancy for Human Immunodeficiency Virus–Infected Women Receiving Efavirenz. Journal of Infectious Diseases. 2017; 217 (6):964-972.

Chicago/Turabian Style

Erika Wallender; Katarina Vučićević; Prasanna Jagannathan; Liusheng Huang; Paul Natureeba; Abel Kakuru; Mary Muhindo; Mirium Nakalembe; Diane Havlir; Moses Kamya; Francesca Aweeka; Grant Dorsey; Philip J Rosenthal; Radojka M Savic. 2017. "Predicting Optimal Dihydroartemisinin-Piperaquine Regimens to Prevent Malaria During Pregnancy for Human Immunodeficiency Virus–Infected Women Receiving Efavirenz." Journal of Infectious Diseases 217, no. 6: 964-972.

Original article
Published: 22 November 2017 in European Journal of General Practice
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Background: During the initiation of treatment of a chronic disease, patients may have varying interests, expectations, concerns, and reasons to stop treatment, influencing compliance with prescribed treatment. Thus, healthcare professionals are expected to integrate these needs into medicines management. Objectives: To determine what information is important to patients; assess predictors of patients’ interests, expectations, concerns, reasons to stop therapy; evaluate drug-related problems following initiation of therapy and summarize how pharmacists resolve them during patient–pharmacist counselling. Methods: In 2014, a four-month study was performed in Serbian community pharmacies, as part of the Pharmaceutical Care Quality Indicators Project led by the European Directorate for the Quality of Medicines & Healthcare. Seventy community pharmacists were asked to participate in the study. Pharmacists recruited adult patients who consented to participate in the study and who initiated treatment, lasting at least six months. Patients completed an open-ended questions form. After two-to-four weeks, a patient–pharmacist consultation was performed. Results: Forty-four community pharmacists (response rate 62.9%) sent back the completed forms from 391 patients (response rate 67.1%). The total number of dispensed drugs was 403. In terms of drug safety, 29.4% of patients sought information, 32.5% expressed concerns, and 28.1% of patients cited it as a reason to discontinue treatment. During the first weeks of therapy, 18% of patients experienced practical problems, while 27.3% reported adverse drug reactions. Conclusion: Safety issues are a major focus of patients’ prescribed new medicines for long-term treatment.

ACS Style

Katarina M. Vučićević; Branislava R. Miljković; Bojana C. Golubović; Marija N. Jovanović; Sandra D. Vezmar Kovačević; Milica D. Ćulafić; Milena Kovačević; Johan J. De Gier. Expectations, concerns, and needs of patients who start drugs for chronic conditions. A prospective observational study among community pharmacies in Serbia. European Journal of General Practice 2017, 24, 19 -25.

AMA Style

Katarina M. Vučićević, Branislava R. Miljković, Bojana C. Golubović, Marija N. Jovanović, Sandra D. Vezmar Kovačević, Milica D. Ćulafić, Milena Kovačević, Johan J. De Gier. Expectations, concerns, and needs of patients who start drugs for chronic conditions. A prospective observational study among community pharmacies in Serbia. European Journal of General Practice. 2017; 24 (1):19-25.

Chicago/Turabian Style

Katarina M. Vučićević; Branislava R. Miljković; Bojana C. Golubović; Marija N. Jovanović; Sandra D. Vezmar Kovačević; Milica D. Ćulafić; Milena Kovačević; Johan J. De Gier. 2017. "Expectations, concerns, and needs of patients who start drugs for chronic conditions. A prospective observational study among community pharmacies in Serbia." European Journal of General Practice 24, no. 1: 19-25.

Journal article
Published: 01 May 2017 in Patient Education and Counseling
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To evaluate elderly polypharmacy patients’ needs and concerns regarding medication through the Structured Patient-Pharmacist Consultation (SPPC). Older patients on chronic treatment with ≥5 medications were asked to fill in the SPPC form at home. A consultation with the community pharmacist, structured according to patient’s answers, followed within 2-4 weeks. Logistic regression associated patients’ individual treatment with care issues and consultation outcomes. Out of 440 patients, 39.5% experienced problems, and 46.1% had concerns about medication use. 122 patients reported reasons for discontinuing treatment. The main outcome of the consultation was a better understanding of medication use (75.5%). Side effects and/or non-adherence were identified in 50% of patients, and 26.6% were referred to the doctor. Atrial fibrillation, COPD, anticoagulants, benzodiazepines, and beta agonists/corticosteroids were associated with problems during medication use. Patients with diabetes improved their understanding of medication use significantly. Patients on benzodiazepines, anticoagulants, and beta agonists/corticosteroids, with atrial fibrillation and/or COPD, may have a higher potential for non-adherence. Counseling patients based on the SPPC model may be particularly useful for patients with diabetes. Practice Implications: The SPPC model is a useful tool for counseling based on patient needs.

ACS Style

Sandra Vezmar Kovačević; Branislava Miljković; Katarina Vucicevic; Milica Ćulafić; Milena Kovačević; Bojana Golubović; Marija Jovanović; Johan J. De Gier. Elderly polypharmacy patients’ needs and concerns regarding medication assessed using the structured patient-pharmacist consultation model. Patient Education and Counseling 2017, 100, 1714 -1719.

AMA Style

Sandra Vezmar Kovačević, Branislava Miljković, Katarina Vucicevic, Milica Ćulafić, Milena Kovačević, Bojana Golubović, Marija Jovanović, Johan J. De Gier. Elderly polypharmacy patients’ needs and concerns regarding medication assessed using the structured patient-pharmacist consultation model. Patient Education and Counseling. 2017; 100 (9):1714-1719.

Chicago/Turabian Style

Sandra Vezmar Kovačević; Branislava Miljković; Katarina Vucicevic; Milica Ćulafić; Milena Kovačević; Bojana Golubović; Marija Jovanović; Johan J. De Gier. 2017. "Elderly polypharmacy patients’ needs and concerns regarding medication assessed using the structured patient-pharmacist consultation model." Patient Education and Counseling 100, no. 9: 1714-1719.

Observational study
Published: 29 March 2017 in Journal of Evaluation in Clinical Practice
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Aims and ObjectivesTargeting older patients with predictive factors for drug-related problems (DRPs) could make clinical medication reviews more cost-effective. The aim of this study was to identify the number, type, and potential predictive factors for DRPs in older polypharmacy patients.MethodsCommunity pharmacists performed clinical medication reviews and documented DRPs, types of interventions, and their implementation in older patients.ResultsThree hundred eighty-eight medication reviews were analyzed, 964 DRPs (average 2.5 ± 1.9), and 1022 interventions (average 2.6 ± 2.0) were identified. The overall implementation rate of interventions was 70.1%, the highest was observed in interventions aiming to resolve the lack of therapy monitoring (86.8%). Patients with ≥12 medications had an increased risk of ≥5 DRPs (P < .001). Asthma was associated with lack of adherence (P = .002), lack of aspirin, statins, and proton pump inhibitors use with additional therapy needed (P = .002-.004). Predictive factors for drug interactions were antihypertensive medications and/or medications with narrow therapeutic index (P < .05). Lack of efficacy was associated with diabetes (P = .006). Nonsteroidal anti-inflammatory drugs were risk factors for inappropriate drug selection (P = .002). Lack of monitoring was associated with hypertension (P = .013), whereas benzodiazepines (P < .001) and aspirin (P = .021) were overused.ConclusionPatients with asthma, hypertension, and diabetes and lack of statin, antithrombotic agent, and/or proton pump inhibitor use were associated with higher risks for DRPs.

ACS Style

Sandra Vezmar Kovačević; Branislava Miljković; Milica Ćulafić; Milena Kovačević; Bojana Golubović; Marija Jovanović; Katarina Vučićević; Johan J. De Gier. Evaluation of drug-related problems in older polypharmacy primary care patients. Journal of Evaluation in Clinical Practice 2017, 23, 860 -865.

AMA Style

Sandra Vezmar Kovačević, Branislava Miljković, Milica Ćulafić, Milena Kovačević, Bojana Golubović, Marija Jovanović, Katarina Vučićević, Johan J. De Gier. Evaluation of drug-related problems in older polypharmacy primary care patients. Journal of Evaluation in Clinical Practice. 2017; 23 (4):860-865.

Chicago/Turabian Style

Sandra Vezmar Kovačević; Branislava Miljković; Milica Ćulafić; Milena Kovačević; Bojana Golubović; Marija Jovanović; Katarina Vučićević; Johan J. De Gier. 2017. "Evaluation of drug-related problems in older polypharmacy primary care patients." Journal of Evaluation in Clinical Practice 23, no. 4: 860-865.

Journal article
Published: 01 September 2016 in Acta Poloniae Pharmaceutica - Drug Research
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Azra Bajraktarevic; Aida Mehmedagic; Katarina Vucicevic; Mehmed Kulic; Branislava Miljkovic. THE POSOLOGY AND TROUGH CONCENTRATIONS OF DIGOXIN IN ADULT AND ELDERLY PATIENTS. Acta Poloniae Pharmaceutica - Drug Research 2016, 73, 1361 -1368.

AMA Style

Azra Bajraktarevic, Aida Mehmedagic, Katarina Vucicevic, Mehmed Kulic, Branislava Miljkovic. THE POSOLOGY AND TROUGH CONCENTRATIONS OF DIGOXIN IN ADULT AND ELDERLY PATIENTS. Acta Poloniae Pharmaceutica - Drug Research. 2016; 73 (5):1361-1368.

Chicago/Turabian Style

Azra Bajraktarevic; Aida Mehmedagic; Katarina Vucicevic; Mehmed Kulic; Branislava Miljkovic. 2016. "THE POSOLOGY AND TROUGH CONCENTRATIONS OF DIGOXIN IN ADULT AND ELDERLY PATIENTS." Acta Poloniae Pharmaceutica - Drug Research 73, no. 5: 1361-1368.

Review
Published: 19 July 2016 in Current Medicinal Chemistry
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Immunosuppressive therapy is the cornerstone of successful kidney transplantation. Frequently used immunosuppressives are cyclosporine, tacrolimus, sirolimus and mycophenolic acid. These drugs have narrow therapeutic index and show high pharmacokinetic variability. In order to maintain the balance between efficacy and safety, dosing is based on measured drug concentrations. Proper identification, quantification and understanding the sources of variability in measured concentrations facilitate routine dose adjustment in clinical practice. Classical pharmacokinetic studies have limited use in transplant patients attributable to design with intense sampling in a small, relatively homogenous population, and identification of only single variability factor per study. Population approach is a powerful tool for analysing sparse data, identifying factors that influence drug pharmacokinetics and estimating variability. In this report we reviewed available population pharmacokinetic models for cyclosporine, tacrolimus, sirolimus and mycophenolic acid in adult kidney transplant patients. The major focus was to describe various demographic factors, biochemical parameters, genetic polymorphisms of metabolic enzymes and transporters and drug-drug interactions, which have been identified as an important concern of pharmacokinetic variability in kidney transplant patients.

ACS Style

Bojana Golubovic; Milica Prostran; Branislava Miljkovic; Katarina Vucicevic; Dragana Radivojevic; Iztok Grabnar. Population Pharmacokinetic Approach of Immunosuppressive Therapy in Kidney Transplant Patients. Current Medicinal Chemistry 2016, 23, 1998 -2011.

AMA Style

Bojana Golubovic, Milica Prostran, Branislava Miljkovic, Katarina Vucicevic, Dragana Radivojevic, Iztok Grabnar. Population Pharmacokinetic Approach of Immunosuppressive Therapy in Kidney Transplant Patients. Current Medicinal Chemistry. 2016; 23 (19):1998-2011.

Chicago/Turabian Style

Bojana Golubovic; Milica Prostran; Branislava Miljkovic; Katarina Vucicevic; Dragana Radivojevic; Iztok Grabnar. 2016. "Population Pharmacokinetic Approach of Immunosuppressive Therapy in Kidney Transplant Patients." Current Medicinal Chemistry 23, no. 19: 1998-2011.

Journal article
Published: 01 November 2015 in Journal of Pharmacy & Pharmaceutical Sciences
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The application of artificial neural networks in the pharmaceutical sciences is broad, ranging from drug discovery to clinical pharmacy. In this study, we explored the applicability of counter-propagation artificial neural networks (CPANNs), combined with genetic algorithm (GA) for prediction of topiramate (TPM) serum levels based on identified factors important for its prediction.

ACS Style

Marija Jovanović; Dragoslav Sokić; Iztok Grabnar; Tomaz Vovk; Milica Prostran; Slavica Erić; Igor Kuzmanovski; Katarina Vučićević; Branislava Miljković. Application of Counter-propagation Artificial Neural Networks in Prediction of Topiramate Concentration in Patients with Epilepsy. Journal of Pharmacy & Pharmaceutical Sciences 2015, 18, 856 -862.

AMA Style

Marija Jovanović, Dragoslav Sokić, Iztok Grabnar, Tomaz Vovk, Milica Prostran, Slavica Erić, Igor Kuzmanovski, Katarina Vučićević, Branislava Miljković. Application of Counter-propagation Artificial Neural Networks in Prediction of Topiramate Concentration in Patients with Epilepsy. Journal of Pharmacy & Pharmaceutical Sciences. 2015; 18 (5):856-862.

Chicago/Turabian Style

Marija Jovanović; Dragoslav Sokić; Iztok Grabnar; Tomaz Vovk; Milica Prostran; Slavica Erić; Igor Kuzmanovski; Katarina Vučićević; Branislava Miljković. 2015. "Application of Counter-propagation Artificial Neural Networks in Prediction of Topiramate Concentration in Patients with Epilepsy." Journal of Pharmacy & Pharmaceutical Sciences 18, no. 5: 856-862.

Journal article
Published: 09 November 2014 in European Journal of Clinical Pharmacology
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The present study aimed to establish population pharmacokinetic model for phenobarbital (PB), examining and quantifying the magnitude of PB interactions with other antiepileptic drugs concomitantly used and to demonstrate its use for individualization of PB dosing regimen in adult epileptic patients.

ACS Style

Katarina Vučićević; Marija Jovanović; Bojana Golubović; Sandra Vezmar Kovačević; Branislava Miljković; Žarko Martinović; Milica Prostran. Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients. European Journal of Clinical Pharmacology 2014, 71, 183 -190.

AMA Style

Katarina Vučićević, Marija Jovanović, Bojana Golubović, Sandra Vezmar Kovačević, Branislava Miljković, Žarko Martinović, Milica Prostran. Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients. European Journal of Clinical Pharmacology. 2014; 71 (2):183-190.

Chicago/Turabian Style

Katarina Vučićević; Marija Jovanović; Bojana Golubović; Sandra Vezmar Kovačević; Branislava Miljković; Žarko Martinović; Milica Prostran. 2014. "Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients." European Journal of Clinical Pharmacology 71, no. 2: 183-190.

Journal article
Published: 01 June 2014 in Open Medicine
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Gentamicin is readily used for suspected or proven sepsis in neonates, yet it shows considerable inter-individual pharmacokinetic variability, which limits achievements of therapeutic levels. Hence, the aim of this study was to compare peak and trough gentamicin concentrations according to dosing regimen, to evaluate pharmacokinetic parameters, and to consider adjustments of dosing regimen. Babies with infection were treated with 1 h infusion, and daily dose of 5 or 7.5 mg/kg depending on the age. Patients were randomized into two groups: I — dosing interval 12 h (n=8), II — 24 h (n=11). Two steady-state blood samples were obtained. Pharmacokinetic parameters were calculated using one-compartment model. The results showed a difference (p

ACS Style

Katarina Vucicevic; Zorica Rakonjac; Borisav Janković; Sandra Vezmar Kovačević; Branislava Miljković; Milica Prostran. Clinical pharmacokinetics in optimal gentamicin dosing regimen in neonates. Open Medicine 2014, 9, 485 -490.

AMA Style

Katarina Vucicevic, Zorica Rakonjac, Borisav Janković, Sandra Vezmar Kovačević, Branislava Miljković, Milica Prostran. Clinical pharmacokinetics in optimal gentamicin dosing regimen in neonates. Open Medicine. 2014; 9 (3):485-490.

Chicago/Turabian Style

Katarina Vucicevic; Zorica Rakonjac; Borisav Janković; Sandra Vezmar Kovačević; Branislava Miljković; Milica Prostran. 2014. "Clinical pharmacokinetics in optimal gentamicin dosing regimen in neonates." Open Medicine 9, no. 3: 485-490.

Research article
Published: 08 May 2014 in Annals of Pharmacotherapy
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Background: Topiramate (TPM) is a sulfamate-substituted monosaccharide that is structurally different from other antiepileptic drugs. TPM inhibits carbonic anhydrase activity, which is associated with loss of bicarbonate from the kidney and consequently metabolic acidosis or electrolyte imbalance. Objective: The objectives of the study were to investigate the influence of TPM therapy on bicarbonate and potassium levels in adult epileptic patients. Methods: Data were collected from 59 adult patients on monotherapy or co-therapy of TPM and other antiepileptic drugs. Serum bicarbonate and potassium levels were available from all patients. Steady-state TPM trough concentrations were determined in blood samples by high-performance liquid chromatography. Data analysis was performed by SPSS software (version 17, Chicago, IL). Results: Patients were divided into group A (duration of therapy shorter than or equal to 5 years) and group B (duration of therapy longer than 5 years). Significant difference ( P < 0.05) in serum bicarbonate levels was observed between these 2 groups. Bicarbonate levels were linearly related to the TPM therapy duration. No correlation was found between the TPM dose or patient age and bicarbonate or potassium levels, as well as between therapy duration and potassium level. Linear regression analysis showed no significant association among 54 available TPM trough concentrations and bicarbonate or potassium levels. Conclusions: Results highlight the frequent occurrence of lower bicarbonate level associated with prolonged TPM therapy. Monitoring bicarbonate levels in patients on long-term TPM therapy might be useful.

ACS Style

Marija Jovanović; Dragoslav Sokić; Iztok Grabnar; Milica Prostran; Radmila Obrenović; Katarina Vučićević; Branislava Miljković. Effect of Long-term Topiramate Therapy on Serum Bicarbonate and Potassium Levels in Adult Epileptic Patients. Annals of Pharmacotherapy 2014, 48, 992 -997.

AMA Style

Marija Jovanović, Dragoslav Sokić, Iztok Grabnar, Milica Prostran, Radmila Obrenović, Katarina Vučićević, Branislava Miljković. Effect of Long-term Topiramate Therapy on Serum Bicarbonate and Potassium Levels in Adult Epileptic Patients. Annals of Pharmacotherapy. 2014; 48 (8):992-997.

Chicago/Turabian Style

Marija Jovanović; Dragoslav Sokić; Iztok Grabnar; Milica Prostran; Radmila Obrenović; Katarina Vučićević; Branislava Miljković. 2014. "Effect of Long-term Topiramate Therapy on Serum Bicarbonate and Potassium Levels in Adult Epileptic Patients." Annals of Pharmacotherapy 48, no. 8: 992-997.