Abstract
Background 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. Methods 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. Results 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). Conclusions These results suggested that rifampicin elevated the plasma concentration of atorvastatin depending on SLCO1B1 genotype and rifampicin pharmacokinetics were not altered by SLCO1B1 genotype.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.