Influence of OATP1B1 Genotype on the Pharmacokinetics of Rosuvastatin in Koreans

• Published in: Clinical pharmacology and therapeutics 2008-02, Vol.83 (2), p.251-257
• Main Authors: Choi, JH, Lee, MG, Cho, J‐Y, Lee, J‐E, Kim, KH, Park, K
• Format: Article
• Language: English
• Subjects: Administration, Oral; Area Under Curve; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Fluorobenzenes - administration & dosage; Fluorobenzenes - blood; Fluorobenzenes - pharmacokinetics; Gene Frequency; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; Korea; Lactones - administration & dosage; Lactones - blood; Lactones - pharmacokinetics; Medical sciences; Organic Anion Transporters - genetics; Organic Anion Transporters - metabolism; Pharmacology. Drug treatments; Phenotype; Polymorphism, Genetic; Pyrimidines - administration & dosage; Pyrimidines - blood; Pyrimidines - pharmacokinetics; Rosuvastatin Calcium; Solute Carrier Organic Anion Transporter Family Member 1b1; Sulfonamides - administration & dosage; Sulfonamides - blood; Sulfonamides - pharmacokinetics
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1038/sj.clpt.6100267

This study was carried out to determine whether polymorphisms of organic anion‐transporting polypeptide 1B1 (OATP1B1) have an effect on rosuvastatin pharmacokinetics in Koreans. Among 200 subjects genotyped for OATP1B1 c.388A>G, and c.521T>C, 30 subjects were selected for the rosuvastatin pharmacokinetic study. The area under the concentration–time curve for 0 to infinity (AUC0–∞) of rosuvastatin for group 1 (*1a/*1a, *1a/*1b, *1b/*1b), group 2 (*1a/*15, *1b/*15), and group 3 (*15/*15) were 111±49.3, 126±45.2, and 191±31.0 ng h/ml, respectively, with significant differences among the three groups (P=0.0429) and between *15/*15 and the other groups (P=0.0181). The maximum plasma concentration (Cmax) also showed a significant difference between *15/*15 and the other groups (P=0.0181). There were no significant differences in rosuvastatin‐lactone pharmacokinetics among the three groups. The pharmacokinetic exposure of rosuvastatin was higher in the OATP1B1*15/*15 subjects than the others, suggesting a potential association between the OATP1B1 genetic polymorphisms and altered rosuvastatin pharmacokinetics in Korean populations. Clinical Pharmacology & Therapeutics (2008) doi:10.1038/sj.clpt.6100267