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

• Published in: Journal of clinical pharmacology 2014-04, Vol.54 (4), p.462-467
• Main Authors: He, Bao-xia, Shi, Lei, Qiu, Jian, Zeng, Xiao-Hui, Zhao, Shu-Jin
• Format: Article
• Language: English
• Subjects: Alleles; Asian Continental Ancestry Group - genetics; Atorvastatin; Cardiovascular disease; Chromatography; Coronary Disease - genetics; Coronary Disease - metabolism; coronary heart disease; CYP3A4; Cytochrome P-450 CYP3A - genetics; genetic polymorphism; Genotype; Genotype & phenotype; Heptanoic Acids - blood; Heptanoic Acids - pharmacokinetics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; Male; Middle Aged; pharmacokinetics; Pyrroles - blood; Pyrroles - pharmacokinetics
• ISSN: 0091-2700; 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.