Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin

Clin Pharmacol Ther. 2007 Dec;82(6):726-33. doi: 10.1038/sj.clpt.6100220. Epub 2007 May 2.

Abstract

Thirty-two healthy volunteers with different SLCO1B1 genotypes ingested a 20 mg dose of atorvastatin and 10 mg dose of rosuvastatin with a washout period of 1 week. Subjects with the SLCO1B1 c.521CC genotype (n=4) had a 144% (P<0.001) or 61% (P=0.049) greater mean area under the plasma atorvastatin concentration-time curve from 0 to 48 h (AUC(0-48 h)) than those with the c.521TT (n=16) or c.521TC (n=12) genotype, respectively. The AUC(0-48 h) of 2-hydroxyatorvastatin was 100% greater in subjects with the c.521CC genotype than in those with the c.521TT genotype (P=0.018). Rosuvastatin AUC(0-48 h) and peak plasma concentration (Cmax) were 65% (P=0.002) and 79% (P=0.003) higher in subjects with the c.521CC genotype than in those with the c.521TT genotype. These results indicate that, unexpectedly, SLCO1B1 polymorphism has a larger effect on the AUC of atorvastatin than on the more hydrophilic rosuvastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Atorvastatin
  • European Continental Ancestry Group / genetics
  • Female
  • Fluorobenzenes / administration & dosage
  • Fluorobenzenes / blood
  • Fluorobenzenes / pharmacokinetics*
  • Genotype
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / blood
  • Heptanoic Acids / pharmacokinetics*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / blood
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Liver / metabolism*
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Organic Anion Transporters / genetics*
  • Organic Anion Transporters / metabolism
  • Polymorphism, Genetic*
  • Prospective Studies
  • Pyrimidines / administration & dosage
  • Pyrimidines / blood
  • Pyrimidines / pharmacokinetics*
  • Pyrroles / administration & dosage
  • Pyrroles / blood
  • Pyrroles / pharmacokinetics*
  • Reference Values
  • Rosuvastatin Calcium
  • Sulfonamides / administration & dosage
  • Sulfonamides / blood
  • Sulfonamides / pharmacokinetics*

Substances

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