Effects of Major Transporter and Metabolizing Enzyme Gene Polymorphisms on Carbamazepine Metabolism in Chinese Patients with Epilepsy

Aim: The present study aimed to evaluate the effects of SNPs of major transporter and metabolizing enzyme genes on carbamazepine (CBZ) metabolism in Chinese patients with epilepsy. Materials & methods: For 210 epileptic patients treated with CBZ as monotherapy, nine SNPs in candidate genes ABCB1, CYP3A4, CYP3A5, POR and EPHX1 were analyzed by PCR-RFLP or direct sequencing. Serum concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC. Dose-adjusted concentrations of CBZ (CDRCBZ), CBZE (CDRCBZE), CBZD (CDRCBZ D) and CBZD:CBZE ratio were used as evaluation parameters for CBZ metabolism. Results: The ABCB1 c.3435C>T was significantly associated with the CDR of CBZ and its major metabolites. CYP3A4*1G and CYP3A5*3 could influence CBZ metabolism, while POR*28 had no effect on it. The EPHX1 c.416A>G and c.128G>C variants were significantly associated with CBZD:CBZE ratio. Conclusion: Our data suggest that certain polymorphisms of major transporter and metabolizing enzyme genes could in part influence interindividual variability of CBZ metabolism in Chinese patients with epilepsy. Original submitted 10 June 2014; Revision submitted 26 September 2014