Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects.
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Kim KA, Park PW, Lee OJ, Kang DK, Park JY
Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects.
J Clin Pharmacol. 2007 Jan;47(1):87-93. doi: 10.1177/0091270006295063.
- PubMed ID
- 17192506 [ View in PubMed]
- 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 x h/mL) was significantly lower than CYP3A5*3/*3 carriers (16.35 +/- 6.37 ng x 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.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Simvastatin Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails Simvastatin Cytochrome P450 3A5 Protein Humans UnknownSubstrateDetails