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.
Trial registration: ClinicalTrials.gov NCT00973986.
Keywords: CYP3A4; coronary heart disease; genetic polymorphism; pharmacokinetics.
© 2013, The American College of Clinical Pharmacology.