Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism

Both 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. Sixteen 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. Rifampicin 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). These results suggested that rifampicin elevated the plasma concentration of atorvastatin depending on SLCO1B1 genotype and rifampicin pharmacokinetics were not altered by SLCO1B1 genotype.