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 pharmiacokinetics 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 C[MAX] but exhibited no significant variations in T[MAX] and ti/[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