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Multidrug resistance proteins (MRP2, ABCC2) may play a role in drug resistance in epilepsy by limiting gastrointestinal absorption and brain access of antiepileptic drugs (AEDs). We sought to investigate the effects of ABCC2 polymorphisms on plasma carbamazepine (CBZ) concentrations and pharmacoresistance in Chinese patients with epilepsy. ABCC2 rs717620, rs2273697, rs3740066 polymorphisms were genotyped by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis or direct automated DNA sequencing in 80 patients treated with CBZ monotherapy. There were no differences in CBZ maintenance doses or adjusted plasma CBZ concentrations among the ABCC2 rs717620, rs2273697 and rs3740066 genotypic groups. No associations between all the studied genotypes and haplotypes involving the three SNPs of ABCC2 and CBZ resistance were observed in this patient cohort. These results suggest that ABCC2 polymorphisms may not contribute to interindividual variabilities in CBZ daily maintenance doses, plasma concentrations, and treatment efficacy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between the CYP3A5 genetic polymorphism and the serum concentrations of carbamazepine (CBZ), to provide guidance for individualized drug dosing. Methods: Eighty-four epilepsy patients taking CBZ were included in this study. Their clinical data were recorded and CBZ serum concentrations were measured. The CYP3A5 6986 genetic polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) assay. Patients were divided according to genotype into CYP3A5 expressor (CYP3A5*1/*1 genotype and CYP3A5*1/*3 genotypes) and non-expressor groups (CYP3A5*3/*3). The two groups were compared for the total dose of CBZ, dose of CBZ/kg body weight, serum drug concentration, dose-corrected serum concentration, and standardized serum concentration. Results: The total dose of CBZ and the dose of CBZ/kg body weight was higher in the CYP3A5 expressor group than the non-expressor (P = 0.043 and P = 0.014, respectively). The dose-corrected and standardized serum concentrations were lower in the CYP3A5 expressor group than the non-expressor (P = 0.001 and P < 0.001, respectively). There was however, no significant difference in serum drug concentration between the two groups (P = 0.487). Conclusions: There was a close relationship between CYP3A5 genetic polymorphism and the serum concentrations of carbamazepine. [ABSTRACT FROM AUTHOR]