Pharmacogenetics of CYP3A5 on Carbamazepine pharmacokinetics in epileptic patients developing toxicity

Mubarak, Al-Gahtany and Gauthaman, Karunakaran and Murali, Munisamy (2014) Pharmacogenetics of CYP3A5 on Carbamazepine pharmacokinetics in epileptic patients developing toxicity. In: From 2nd International Genomic Medical Conference (IGMC 2013.

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Abstract

Background The genetically polymorphic cytochrome P450 enzymes are involved in the metabolism and elimination of a number of widely used drugs. CYP3A5 exhibits remarkable inter-individual differences in the pharmacokinetics of Carbamazepine [1]. The present study was undertaken to investigate the effects of CYP3A5 on the pharmacokinetics of antiepileptic drug Carbamazepine in the epileptic patients showing toxicity. Materials and methods 30 epileptic individuals who had developed toxicity to carbamazepine and 30 control epileptic subjects who had not developed toxicity to carbamazepine were genotyped for CYP3A5 polymorphisms by polymerase chain reactionrestriction fragment length polymorphisms (PCR-RFLP Method). Carbamazepine plasma levels were analyzed by reversed phase HPLC method and pharmacokinetic parameters such as area under the concentration curve (AUC), maximum concentration (Cmax), time to Cmax (tmax) and half-life (t1/2) were estimated by non-compartmental analysis using PK SOLUTIONS® software. Results A significant correlation was observed in the frequency of homozygous CYP3A5 mutant allele (P <0.01) among the carbamazepine toxicity and controls. The pharmacokinetics parameters of carbamazepine in homozygous mutant group showed longer half-life (t ½ = 17 hrs) andless clearance rate (CL =1.5 L/hr) when compared to wild type group ( t ½ =12.8 hrs, CL = 2.9 L/hr). Conclusions Our findings suggest that the CYP3A5 Genetic Polymorphisms plays a significant role in the steady state concentrations of carbamazepine and thereby having impact on toxicity in epileptic patients.

Item Type: Conference or Workshop Item (Poster)
Subjects: Medicine and Surgery
Pharmaceutical Sciences
Pharmacy
Biology
Divisions: College of Pharmacy > Pharmacy
Depositing User: GAUTHAMAN Karunakaran
Date Deposited: 06 Mar 2017 09:56
Last Modified: 06 Mar 2017 09:56
URI: http://eprints.kku.edu.sa/id/eprint/484

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