Effects of CYP3A4*1G and CYP3A5*3 polymorphisms on pharmacokinetics of tylerdipine hydrochloride in healthy Chinese subjects. (4th March 2019)

• Record Type: Journal Article
• Authors: Zhou, Sufeng; Tao, Mingxue; Wang, Yuanyuan; Wang, Lu; Xie, Lijun; Chen, Juan; Zhao, Yuqing; Liu, Yun; Zhang, Hongwen; Ou, Ning; Wang, Guangji; Shao, Feng; Aa, Jiye
• Is Part Of: Xenobiotica. Volume 49:Number 3(2019:Mar.)
• Page Start: 375
• Page End: 380
• Publication Date: 2019-03-04
• Subjects: Tylerdipine hydrochloride -- pharmacokinetics -- CYP3A4*1G -- CYP3A5*3 -- polymorphism -- healthy Chinese subjects; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2018.1447711
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: 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 (AUC0–24 h ) were all corrected by the dose given. In the wild-type group, the mean dose-corrected AUC0–24 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 AUC0–24 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.