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

Author(s)
Tausif Ahmed Rajput Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University,Islamabad,Pakistan
Abdul Khaliq Naveed Biochemistry, Islamic International Medical College-TRUST, Riphah International University,Islamabad,Pakistan
Zia-Ur-Rehman Farooqi Department of Medical Technology, Shifa Tameer-e-Millat University,Islamabad,Pakistan
Shakir Khan Department of Biochemistry, Margalla Institute of Health Sciences,Rawalpindi,Pakistan
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.
Publication Details
Page(s) 1363-1370
DOI DOI not available
Published Journal: Pakistan Journal of Pharmaceutical Sciences, Volume: 30, Issue: 4, Year: 2017

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Keywords
single nucleotide polymorphism, Pharmacokinetics, SLCO1B1, OATP1B1
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