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

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.