Different Effects of SLCO1B1 Polymorphism on the Pharmacokinetics of Atorvastatin and Rosuvastatin

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 ( C max ) 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. Clinical Pharmacology & Therapeutics (2007) 82 , 726–733. doi: 10.1038/sj.clpt.6100220 ; published online 2 May 2007