The effect of CYP3A4*1G allele on the pharmacokinetics of atorvastatin in Chinese Han patients with coronary heart disease

J Clin Pharmacol. 2014 Apr;54(4):462-7. doi: 10.1002/jcph.229. Epub 2013 Nov 27.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human

Associated data

  • ClinicalTrials.gov/NCT00973986