Influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphism on dose-adjusted plasma levels of carbamazepine in epileptic patients in South Indian population

AIM: The aim of the study was to compare the dose-adjusted plasma levels of carbamazepine (CBZ) among expressers and nonexpressers of cytochrome P450 3A5 (CYP3A5)* 3 genotypes. SUBJECTS AND METHODS: The study was carried out in 100 epileptic patients who were on CBZ monotherapy. Steady-state plasma CBZ levels were measured using reverse-phase high-performance liquid chromatography method, and genotyping of CYP3A5 was done using real-time polymerase chain reaction method. RESULTS: Patients inheriting CYP3A5*3/*3 variant (nonexpressers) had an increased plasma concentration of CBZ (4.86 μg/ml) when compared to patients inheriting either CYP3A5*1/*1 or CYP3A5*1/*3 (expressers) (4.3 μg/ml, P = 0.004). Nonexpressers had significantly increased plasma concentrations of CBZ when adjusted for dose and weight when compared to expressers (P < 0.002 and P < 0.001, respectively). The frequency of adverse reactions in expressers and nonexpressers was 12% and 9%, respectively. CONCLUSION: There is a significant influence of CYP3A5*3 genetic polymorphism (6986A>G) on dose-adjusted plasma levels of CBZ in epileptic patients in the South Indian population.