Different Effects of the ABCG2 C.421C>A SNP on the Pharmacokinetics of Fluvastatin, Pravastatin and Simvastatin
- 20 October 2009
- journal article
- Published by Taylor & Francis Ltd in Pharmacogenomics
- Vol. 10 (10), 1617-1624
- https://doi.org/10.2217/pgs.09.85
Abstract
Aims: This study aimed to investigate possible effects of the ABCG2 c.421C>A (p.Gln141Lys; rs2231142) genotype on fluvastatin, pravastatin and simvastatin pharmacokinetics. Materials & methods: In a crossover study, five healthy volunteers with the ABCG2 c.421A/A genotype, four with the c.421C/A genotype and 23 with the c.421C/C genotype ingested a single 40-mg dose of fluvastatin, pravastatin and simvastatin, with a washout period of 1 week. Plasma statin concentrations were measured up to 12 h. Results: The estimated marginal mean area under the plasma concentration–time curve from 0 h to infinity (AUC0–∞) of fluvastatin was 97% (p = 0.015) or 72% (p = 0.009) larger in participants with the A/A genotype than in those with the C/A or C/C genotype. The AUC0–∞ of simvastatin lactone was 111% (p = 0.005) larger in participants with the A/A genotype than in participants with the C/C genotype. The simvastatin acid:lactone AUC0–∞ ratio was 46% (p = 0.017) smaller in individuals with the A/A genotype than in th...Funding Information
- Sigrid Juselius Foundation
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