<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08), indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26), higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47) and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79) of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed.</p></abstract>

Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08), indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26), higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47) and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79) of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed.

CYP3A5 Polymorphism In Serbian Paediatric Epileptic Patients On Carbamazepine Treatment

Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia

Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Serbia

Department of Paediatrics, Faculty of Medical Sciences, University of Kragujevac, Serbia

Experimental and Applied Biomedical Research (EABR)

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

POLIMORFIZAM CYP3A5 KOD DECE SA EPILEPSIJOM LEČENE KARBAMAZEPINOM U SRBIJI

Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of...

CYP3A5 Polymorphism In Serbian Paediatric Epileptic Patients On Carbamazepine Treatment

Online veröffentlicht: 27. Juni 2015

Seitenbereich: 93 - 99

Eingereicht: 03. Nov. 2014

Akzeptiert: 23. Apr. 2015

DOI: https://doi.org/10.1515/sjecr-2015-0012

Schlüsselwörter
CYP3A5 polymorphism, Serbian, epilepsy, carbamazepine

© Dragana Dragas Milovanovic et al.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

CYP3A5 Polymorphism In Serbian Paediatric Epileptic Patients On Carbamazepine Treatment

Online veröffentlicht: 27. Juni 2015

Seitenbereich: 93 - 99

Eingereicht: 03. Nov. 2014

Akzeptiert: 23. Apr. 2015

DOI: https://doi.org/10.1515/sjecr-2015-0012

SchlüsselwörterCYP3A5 polymorphism, Serbian, epilepsy, carbamazepine

© Dragana Dragas Milovanovic et al.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Schlüsselwörter
CYP3A5 polymorphism, Serbian, epilepsy, carbamazepine