Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects

Kyoung Ah Kim, Pil Whan Park, Ock Je Lee, Dong Kyun Kang, Ji-Young Park

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Abstract

Simvastatin, a cholesterol-lowering agent, is mainly metabolized by CYP3A4/5. The objective of this study was to investigate the effect of CYP3A5*3 genotype on the pharmacokinetics of simvastatin in humans. Twenty-two men with CYP3A5*1/*1 (n = 4), CYP3A5*1/*3 (n = 8), or CYP3A5*3/*3 (n = 10) genotypes were enrolled. Each subject ingested a 20-mg dose of simvastatin, and plasma simvastatin concentrations were measured for 12 hours after dosing. The mean (±SD) area under the plasma concentration-time curve for simvastatin in the CYP3A5*1/*1 carriers (4.94 ± 2.25 ng·h/mL) was significantly lower than CYP3A5*3/*3 carriers (16.35 ± 6.37 ng·h/mL; P =.013, Bonferroni test). The mean (±SD) oral clearance was also significantly different between CYP3A5*1/*1 carriers (4.80 ± 2.35 L/h) and CYP3A5*3/*3 carriers (1.35 ± 0.61 L/h; P <.05, Dunn's test). However, other pharmacokinetic parameters including peak plasma concentrations and half-life did not show any difference between genotype groups. These findings suggest that the polymorphic CYP3A5 gene affects the disposition of simvastatin and provides a plausible explanation for interindividual variability of simvastatin disposition.

Original languageEnglish
Pages (from-to)87-93
Number of pages7
JournalJournal of Clinical Pharmacology
Volume47
Issue number1
DOIs
Publication statusPublished - 2007 Jan 1

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Keywords

  • CYP3A5*3
  • Cytochrome P450 3A5 (CYP3A5)
  • Pharmacogenetics
  • Pharmacokinetics
  • Simvastatin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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