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

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) 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 CYP3A4*1G 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 CYP3A5*3/*3 genotype, the mean t was 1.35-fold higher than in CYP3A5*1/*1 group (p = .007). And the t 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.

The Genetic Polymorphisms of CYP3A4*1G and CYP3A5*3 in Javanese Indonesian Population

“…Individuals with CYP3A4*1G showed variations in the pharmacokinetic profiles of fentanyl, tacrolimus, diltiazem, sufentanil, and tylerdipine hydrochloride [5][6][7][8][9]. An increased risk of breast cancer occurrence is known to be associated with CYP3A4*1G polymorphism [10].…”

Cyp3A4 *1G polymorphism is associated with alcohol drinking: A 5-year retrospective single centered population-based study in China

“…Genetic factors are known to be responsible for the variability in the CYP3A4 activity [6,7]. CYP3A4*1G (IVS10+12G >A, rs2242480) is a single nucleotide polymorphism site with a high mutation frequency in Chinese population, which includes wild-type homozygote (CYP3A4*1/*1, GG), mutant heterozygote (CYP3A4*1/*1G, GA), and mutant homozygote (CYP3A4*1G/*1G, AA) [8][9][10]. A synonymous G-A transition has been confirmed to be associated with CYP3A4 enzyme activity, which decrease metabolism of clinical drugs and requires distinct treatment among different patients [10,11].…”

Impact of CYP3A4*1G Polymorphism on Fentanyl Analgesia Assessed by Analgesia Nociception Index in Chinese Patients Undergoing Hysteroscopy

“…[ 8 9 10 ] Among CYP3A4 alleles identified, CYP3A4*1G (CYP3A4 SNP, rs2242480 [G/A]) is a well-known single-nucleotide polymorphism site with a high mutation frequency in Chinese population. [ 11 12 13 14 ] A synonymous G-A transition in exon 10 has been confirmed to be associated with CYP3A4 enzyme activity, leading to change in drug metabolism and distinct response to treatment among different patients. CYP3A4*1G genetic polymorphism has been found to decrease fentanyl consumption and sufentanil consumption for postoperative pain control.…”