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 CYP3A41G and CYP3A53 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 CYP3A41G and CYP3A53, 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) and the area under the curve (AUC) were all corrected by the dose given. In the wild-type group, the mean dose-corrected AUC was 1.35-fold larger than in CYP3A41G carriers (p = .018). Among the three CYP3A5 genotypes, there showed significantly difference (p = .008) in the t, but no significant difference was observed for the AUC and C. In subjects with the CYP3A53/3 genotype, the mean t was 1.35-fold higher than in CYP3A51/1 group (p = .007). And the t in CYP3A53 carriers also was 1.32-fold higher than in the wild-type group (p = .004). CYP3A41G and CYP3A53 polymorphisms may influence tylerdipine pharmacokinetic in healthy Chinese subjects.