Effects of CYP3A4*1G and CYP3A5*3 polymorphisms on pharmacokinetics of tylerdipine hydrochloride in healthy Chinese subjects
Creators: name: Zhou, Sufeng
name: Tao, Mingxue
name: Wang, Yuanyuan
name: Wang, Lu
name: Xie, Lijun
name: Chen, Juan
name: Zhao, Yuqing
name: Liu, Yun
name: Zhang, Hongwen
name: Ou, Ning
name: Wang, Guangji
name: Shao, Feng
name: Aa, Jiye
Publisher: name: Taylor & Francis
Year: 2018
Subjects: subject: Biophysics
subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Neuroscience
subject: Physiology
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Mental Health

description: 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 (<i>C</i><sub>max</sub>) and the area under the curve (AUC<sub>0–24 h</sub>) were all corrected by the dose given.In the wild-type group, the mean dose-corrected AUC<sub>0–24 h</sub> was 1.35-fold larger than in CYP3A4*1G carriers (<i>p</i> = .018). Among the three CYP3A5 genotypes, there showed significantly difference (<i>p</i> = .008) in the <i>t</i><sub>1/2</sub>, but no significant difference was observed for the AUC<sub>0–24 h</sub> and <i>C</i><sub>max</sub>. In subjects with the CYP3A5*3/*3 genotype, the mean <i>t</i><sub>1/2</sub> was 1.35-fold higher than in CYP3A5*1/*1 group (<i>p</i> = .007). And the <i>t</i><sub>1/2</sub> in CYP3A5*3 carriers also was 1.32-fold higher than in the wild-type group (<i>p</i> = .004).CYP3A4*1G and CYP3A5*3 polymorphisms may influence tylerdipine pharmacokinetic 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 (<i>C</i><sub>max</sub>) and the area under the curve (AUC<sub>0–24 h</sub>) were all corrected by the dose given. In the wild-type group, the mean dose-corrected AUC<sub>0–24 h</sub> was 1.35-fold larger than in CYP3A4*1G carriers (<i>p</i> = .018). Among the three CYP3A5 genotypes, there showed significantly difference (<i>p</i> = .008) in the <i>t</i><sub>1/2</sub>, but no significant difference was observed for the AUC<sub>0–24 h</sub> and <i>C</i><sub>max</sub>. In subjects with the CYP3A5*3/*3 genotype, the mean <i>t</i><sub>1/2</sub> was 1.35-fold higher than in CYP3A5*1/*1 group (<i>p</i> = .007). And the <i>t</i><sub>1/2</sub> in CYP3A5*3 carriers also was 1.32-fold higher than in the wild-type group (<i>p</i> = .004). CYP3A4*1G and CYP3A5*3 polymorphisms may influence tylerdipine pharmacokinetic in healthy Chinese subjects.