Influence of OATP1B1 genotype on the pharmacokinetics of rosuvastatin in Koreans

Clin Pharmacol Ther. 2008 Feb;83(2):251-7. doi: 10.1038/sj.clpt.6100267. Epub 2007 Jun 13.

Abstract

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 (AUC(0-infinity)) 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Area Under Curve
  • Asian Continental Ancestry Group / genetics*
  • 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*
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters / genetics*
  • Organic Anion Transporters / metabolism
  • Phenotype
  • Polymorphism, Genetic*
  • Pyrimidines / administration & dosage
  • Pyrimidines / blood
  • Pyrimidines / pharmacokinetics*
  • Rosuvastatin Calcium
  • Sulfonamides / administration & dosage
  • Sulfonamides / blood
  • Sulfonamides / pharmacokinetics*

Substances

  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lactones
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • Pyrimidines
  • SLCO1B1 protein, human
  • Sulfonamides
  • Rosuvastatin Calcium