ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin

Jenni Keskitalo, O Zolk, Martin F Fromm, Kaisa Kurkinen, Pertti J Neuvonen, Mikko Niemi

    Research output: Contribution to journalArticleScientificpeer-review


    "The ABCG2 c.421C> A single-nucleotide polymorphism (SNP) was determined in 660 healthy Finnish volunteers, of whom 32 participated in a pharmacokinetic crossover study involving the administration of 20 mg atorvastatin and rosuvastatin. The frequency of the c.421A variant allele was 9.5% (95% confidence interval 8.1-11.3%). Subjects with the c.421AA genotype (n = 4) had a 72% larger mean area under the plasma atorvastatin concentration-time curve from time 0 to infinity (AUC(0-infinity)) than individuals with the c.421CC genotype had (n = 16; P = 0.049). In participants with the c.421AA genotype, the rosuvastatin AUC(0-infinity) was 100% greater than in those with c.421CA (n = 12) and 144% greater than in those with the c.421CC genotype. Also, those with the c.421AA genotype showed peak plasma rosuvastatin concentrations 108% higher than those in the c.421CA genotype group and 131% higher than those in the c.421CC genotype group (P = 0.01). In MDCKII-ABCG2 cells, atorvastatin transport was increased in the apical direction as compared with vector control cells (transport ratio 1.9 +/- 0.1 vs. 1.1 +/-0.1). These results indicate that the ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and, even more so, of rosuvastatin-potentially affecting the efficacy and toxicity of statin therapy."
    Original languageEnglish
    JournalClinical Pharmacology and Therapeutics
    Issue number2
    Pages (from-to)197-203
    Number of pages7
    Publication statusPublished - 2009
    MoE publication typeA1 Journal article-refereed

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