ABCB1 haplotypes differentially affect the pharmacokinetics of the acid and lactone forms of simvastatin and atorvastatin.

ABCB1 haplotypes were determined in 534 healthy Finnish volunteers, of whom 24 participated in a pharmacokinetic study on simvastatin and atorvastatin. The frequencies of occurrence of haplotypes c.1236T-c.2677T-c.3435T and c.1236C-c.2677G-c.3435C were 42.7 and 34.4%, respectively. The simvastatin acid AUC(0-12h) was 60% larger, the atorvastatin AUC(0-infinity) 55% larger, and the atorvastatin half-life 24% longer in subjects with the ABCB1 TTT/TTT genotype (n = 12) than in those with the CGC/CGC genotype (n = 12) (P < 0.05), but there were no differences between the two genotypes with respect to the pharmacokinetics of the lactones of these drugs.