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

Abstract

1. 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.

2. 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.

3. 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).

4. CYP3A4*1G and CYP3A5*3 polymorphisms may influence tylerdipine pharmacokinetic in healthy Chinese subjects.

Keywords:

• Tylerdipine hydrochloride
• pharmacokinetics
• CYP3A4*1G
• CYP3A5*3
• polymorphism
• healthy Chinese subjects

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This study was funded by XuanZhu Pharma Co., Ltd. (Jinan, China).