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Different Effects of SLCO1B1 Polymorphism on the Pharmacokinetics of Atorvastatin and Rosuvastatin
Author(s) -
Pasanen M K,
Fredrikson H,
Neuvonen P J,
Niemi M
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100220
Subject(s) - slco1b1 , rosuvastatin , atorvastatin , genotype , pharmacokinetics , cmax , pharmacology , medicine , pharmacogenetics , statin , rosuvastatin calcium , chemistry , biochemistry , gene
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