Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin.
Clin Pharmacol Ther
; 82(6): 726-33, 2007 Dec.
Article
in En
| MEDLINE
| ID: mdl-17473846
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Pyrimidines
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Pyrroles
/
Sulfonamides
/
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/
Organic Anion Transporters
/
Fluorobenzenes
/
Heptanoic Acids
/
Liver
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
Clin Pharmacol Ther
Year:
2007
Document type:
Article
Affiliation country:
Finlandia