The influence of CYP3A5 ＊ 3 and BCRPC421A genetic polymorphisms on the pharmacokinetics of felodipine in healthy Chinese volunteers

摘要

Aim The aim of this study was to evaluate the pharmacogenetic variability in the disposition of felodip- ine in healthy Chinese subjects. Methods A single oral dose of 5 mg felodipine was orally administered to 45 healthy Chinese subjects. The serum concentrations of felodipine were measured by using LC/MS/MS. We detected the SNPs of CYP450 enzymes and transporters, which play vital roles in drug metabolism and are with a high fre- quency of mutation in Chinese. Results The area under the plasma concentration - time curve （AUC） within the time points 0 to 72 h （AUC（0-72） ） after felodipine administration was significantly higher in the subjects possessing the CYP3A5 ＊ 1/＊ 3 alleles than in those with the CYP3A5 ＊ 1/＊ 1 alleles （P =0. 021 ）. The BCRP 421A allele was associated with a trend of reduced pharmacokinetic exposure （P = 0. 034）. The mean Tmax in subjects with the CYP3A4 ＊ 1/＊ 18B carriers was longer than in those with the CYP3A4 ＊ 1/＊ 1. The pharmacokinetics charac- teristics of felodipine were not associated with other SNPs we investigated. Conclusion This study showed that the genetic polymorphisms of CYP3A5＊ 3 and BCRPC421A might explain the variability in the pharmacokinetics of felodipine in the Chinese population.