Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism.
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.
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, 410078, China.
Yi-Jing
YJ
He
Wei
W
Zhang
Yao
Y
Chen
Dong
D
Guo
Jiang-Hua
JH
Tu
Lin-Yong
LY
Xu
Zhi-Rong
ZR
Tan
Bi-Lian
BL
Chen
Zhi
Z
Li
Gan
G
Zhou
Bang-Ning
BN
Yu
Julia
J
Kirchheiner
Hong-Hao
HH
Zhou
D000069059:Atorvastatin; D005838:Genotype; D006538:Heptanoic Acids / Q000097:blood*; D006801:Humans; D007700:Kinetics; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011758:Pyrroles / Q000097:blood*; D012293:Rifampin / Q000097:blood* / Q000493:pharmacokinetics; D013936:Thymidine / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D006538:Heptanoic Acids; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D011758:Pyrroles; C503999:SLCO1B1 protein, human; D000069059:Atorvastatin; D013936:Thymidine; D012293:Rifampin