Article ID Journal Published Year Pages File Type
1966612 Clinica Chimica Acta 2009 4 Pages PDF
Abstract

BackgroundBoth atorvastatin and rifampicin are substrates of OATP1B1 (organic anion transporting polypeptide 1B1) encoded by SLCO1B1 gene. Rifampicin is a potent inhibitor of SLCO1B1 (IC50 1.5 umol/l) and SLCO1B1 521T>C functional genetic polymorphism alters the kinetics of atorvastatin in vivo. We hypothesize that rifampicin might influence atorvastatin kinetics in a SLCO1B1 polymorphism dependent manner.MethodsSixteen subjects with known SLCO1B1 genotypes (6 c.521TT, 6 c.521TC and 4 c.521CC) were divided into 2 groups (atorvastatin–placebo group, n = 8; atorvastatin–rifampicin group, n = 8) randomly. In this 2-phase crossover study, atorvastatin (40 mg single-oral dose) pharmacokinetics after co-administration of placebo and rifampicin (600 mg single-oral dose) were measured for up to 48 h by liquid chromatography–mass spectrometry (LC–MS). In the third phase, rifampicin (450 mg single-oral dose) pharmacokinetics was measured additionally.ResultsRifampicin increased atorvastatin plasma concentration in accordance with SLCO1B1 521T>C genotype while the increasing percentage of AUC(0–48) among c.521TT, c.521TC and c.521CC individuals were 833 ± 245% vs 468 ± 233% vs 330 ± 223% (P = 0.007). However, SLCO1B1 521T>C exerted no impact on rifampicin pharmacokinetics (P > 0.05).ConclusionsThese results suggested that rifampicin elevated the plasma concentration of atorvastatin depending on SLCO1B1 genotype and rifampicin pharmacokinetics were not altered by SLCO1B1 genotype.

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Biochemistry
Authors
, , , , , , , , , , , , ,