Effects of CYP3A4*1G and CYP3A5*3 polymorphisms on pharmacokinetics of tylerdipine hydrochloride in healthy Chinese subjects

The aim of this analysis was to explore the influence of CYP3A4*1G and CYP3A5*3 polymorphisms on the pharmacokinetics of tylerdipine in healthy Chinese subjects. A total of 64 and 63 healthy Chinese subjects were included and identified as the genotypes of CYP3A4*1G and CYP3A5*3, respectively. Plasma samples were collected for up to 120 h post-dose to characterize the pharmacokinetic profile following single oral dose of the drug (5, 15, 20, 25 and 30 mg). Plasma levels were measured by a high-performance liquid chromatography-mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated using non-compartmental method. The maximum concentration (C _max ) and the area under the curve (AUC _{0–24 h} ) were all corrected by the dose given. In the wild-type group, the mean dose-corrected AUC _{0–24 h} was 1.35-fold larger than in CYP3A4*1G carriers (p =.018). Among the three CYP3A5 genotypes, there showed significantly difference (p =.008) in the t _1/2 , but no significant difference was observed for the AUC _{0–24 h} and C _max . In subjects with the CYP3A5*3/*3 genotype, the mean t _1/2 was 1.35-fold higher than in CYP3A5*1/*1 group (p =.007). And the t _1/2 in CYP3A5*3 carriers also was 1.32-fold higher than in the wild-type group (p =.004). CYP3A4*1G and CYP3A5*3 polymorphisms may influence tylerdipine pharmacokinetic in healthy Chinese subjects.