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

• Published in: Indian journal of pharmacology Vol. 51; no. 6; pp. 384 - 388
• Main Authors: Ganesapandian, Mahalakshmi, Ramasamy, Kesavan, Adithan, Surendiran, Narayan, Sunil
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.11.2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Wolters Kluwer - Medknow
• Subjects: African Americans; Anticonvulsants; Carbamazepine; Chromatography; Convulsions & seizures; Cytochrome; Drug dosages; Enzymes; Epilepsy; Genetic aspects; Genetic polymorphisms; Genetic research; Genotypes; High performance liquid chromatography; Liquid chromatography; Metabolism; Minority & ethnic groups; Polymerase chain reaction; Polymorphism; Population; Primidone; Sample size; Statistical analysis; Studies; Time; United States > US; cytochrome P450 3A5; genetic polymorphisms; Carbamazepine; pharmacogenetics
• ISSN: 0253-7613; 1998-3751; 1998-3751
• DOI: 10.4103/ijp.IJP_122_19

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.