Effects of two functionally important SLCO1B1 gene polymorphisms on pharmacokinetics of atorvastatin

Abstract

Organic anion transporter polypeptide 1B1 (OATP1B1) encoded by (SLCO1B1) gene, an uptake transporter involved in the transport of drugs and endogenous compounds and located in hepatocyte sinusoidal membrane. Objective of study was to investigate the effects of two functionally significant SNPs (388A>G and 521T>C) and their respective genotypes of SLCO1B1 gene encoding OATP1B1 on the pharmacokinetics of atorvastatin. A total of 100 subjects divided into 6 groups as per their genotype profile were recruited. A single dose of 80mg atorvastatin was orally administered and plasma concentration measured up to 48 hours. The 388A>G and 521T>C genotypes were significantly associated with each other when compared for AUC and Cmax but exhibited no significant variations in Tmax and t1/2. 521 SNP is rather more strongly associated with altered pharmacokinetics of atorvastatin when compared with the 388 SNP, though the homozygous bi-allelic variant of 388 SNP also exhibited a fairly significant variation along with homozygous bi-allelic variant of 521 SNP. The inter-individual variation in pharmacokinetics can be explained by SLCO1B1 polymorphism.