alexa Different effects of the ABCG2 c.421C>A SNP on the pharmacokinetics of fluvastatin, pravastatin and simvastatin.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacogenomics & Pharmacoproteomics

Author(s): Keskitalo JE, Pasanen MK, Neuvonen PJ, Niemi M

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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 (AUC(0-infinity)) 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 AUC(0-infinity) 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 AUC(0-infinity) ratio was 46\% (p = 0.017) smaller in individuals with the A/A genotype than in those with the C/C genotype. The ABCG2 genotype had no significant effect on simvastatin acid or pravastatin pharmacokinetics. CONCLUSIONS: Genetic variability in ABCG2 markedly affects the pharmacokinetics of fluvastatin and simvastatin lactone, but has no significant effect on pravastatin or active simvastatin acid. Genotyping for ABCG2 in addition to SLCO1B1 and ABCB1 polymorphisms could help in predicting statin pharmacokinetics when selecting a statin and its dose for an individual patient. This article was published in Pharmacogenomics and referenced in Journal of Pharmacogenomics & Pharmacoproteomics

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