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.
Keskitalo
J E
JE
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Kurkinen
K J
KJ
Neuvoneni
P J
PJ
Niemi
M
M
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D019540:Area Under Curve; D000069059:Atorvastatin; D018592:Cross-Over Studies; D005260:Female; D005387:Finland; D006207:Half-Life; D006239:Haplotypes; D006538:Heptanoic Acids / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D007783:Lactones / Q000493:pharmacokinetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000493:pharmacokinetics*; D019821:Simvastatin / Q000493:pharmacokinetics*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007783:Lactones; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin