The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
ABCG2 Polymorphism Markedly Affects the Pharmacokinetics of Atorvastatin and Rosuvastatin
Abstract
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 < or = 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.
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Cites
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Importance of P-glycoprotein at blood–tissue barriers
Fromm, M. F. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.06.002 · Cited by 592
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Metadata
- Authors
- Keskitalo, J. E., Zolk, O., Fromm, M. F., Kurkinen, K. J., Neuvonen, P. J., & Niemi, M.
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2009-05-27
- Volume
- 86
- Issue
- 2
- Pages
- 197-203
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W2141941946
- Cited by
- 416
- References
- 3
- FWCI
- 22.65
- Type
- journal article
- Language
- en
- Open access
- closed
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