The effect of CYP3A41G allele on the pharmacokinetics of atorvastatin in Chinese Han patients with coronary heart disease

• Published in: Journal of clinical pharmacology Vol. 54; no. 4; p. 462
• Main Authors: He, Bao-Xia, Shi, Lei, Qiu, Jian, Zeng, Xiao-Hui, Zhao, Shu-Jin
• Format: Journal Article
• Language: English
• Published: England 01.04.2014
• Subjects: Alleles; Asian Continental Ancestry Group - genetics; Atorvastatin; Coronary Disease - genetics; Coronary Disease - metabolism; Cytochrome P-450 CYP3A - genetics; Genotype; Heptanoic Acids - blood; Heptanoic Acids - pharmacokinetics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; Male; Middle Aged; Pyrroles - blood; Pyrroles - pharmacokinetics; pharmacokinetics; coronary heart disease; CYP3A4; genetic polymorphism
• ISSN: 1552-4604
• DOI: 10.1002/jcph.229

The present study aimed to evaluate the impact of CYP3A4*1G allele on the pharmacokinetics of atorvastatin in the Chinese Han patients with coronary heart disease (CHD). Twenty male patients of CHD with different CYP3A4*1G genotypes were orally administered a single 20 mg dose of atorvastatin. Plasma concentrations of atorvastatin and 2-hydroxyatorvastatin were measured by high-performance liquid chromatography tandem mass spectrometry. The mean area under the plasma concentration-time curve from 0 to infinity (AUC0-∞ ) of atorvastatin in subjects with the CYP3A4*1G/*1G genotype were 36% or 25% lower than in those with the wild-type or the *1/*1G genotype, respectively. The time to peak plasma concentration (Tmax ) and oral clearance of atorvastatin (CL/F) were significantly different between subjects with the CYP3A4*1G/*1G genotype and the wild-type. The AUC0-∞ for 2-hydroxyatorvastatin in subjects with the CYP3A4*1G/*1G genotype was 44% or 31% lower than in those with the wild-type or the *1/*1G genotype, respectively. The peak plasma concentration, Tmax and apparent clearance of 2-hydroxyatorvastatin (CL/Fm) were significantly different between subjects with the CYP3A4*1G/*1G genotype and the wild-type. This study indicates that the CYP3A4*1G allele is associated with the pharmacokinetics of atorvastatin and its metabolites in those Chinese Han patients with CHD after a single oral dose.