title: [Genetic polymorphisms of SLCO1B1 for drug pharmacokinetics and its clinical implications].
abstract: Various drug transporters are selectively expressed in single or multiple tissues, such as the intestine, liver and kidney, where these transporters play various roles in drug absorption, distribution and excretion. Genetic polymorphisms in drug transporters as well as drug-metabolizing enzymes are associated with interindividual differences in drug disposition, efficacy and toxicity. Organic anion transporting polypeptide 1B1 (OATP1B1, gene SLCO1B1) is expressed on the basolateral membrane of hepatocytes and can facilitate hepatic uptake of certain clinically relevant drugs such as statins except for fluvastatin, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, antidiabetic drug (repaglinide) and anticancer drugs (SN-38 and methotrexate). Some single nucleotide polymorphisms or haplotypes of the SLCO1B1 gene have been identified and demonstrated to have functional significance for transporter activity. For examples, the SLCO1B1*15 haplotype (or 521T>C genotype) results in decreased uptake activity of SN-38 from systemic circulation, leading to increased plasma concentration of SN-38 and an enhanced risk of neutropenia. This review focuses on the impact of genetic polymorphisms of the SLCO1B1 gene on transport activity, and implications for the clinical efficacy and toxicity of clinically useful drugs.
authors: Department of Hospital Pharmacy, Faculty of Medicine, Tottori University, Tottori, Japan. takane@med.tottori-u.ac.jp
authors: Hiroshi
authors: H
authors: Takane
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000493:pharmacokinetics; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics; D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D002219:Carbamates / Q000493:pharmacokinetics; D006239:Haplotypes; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics; D000077146:Irinotecan; D008099:Liver / Q000378:metabolism; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D010597:Pharmacogenetics; D010880:Piperidines / Q000493:pharmacokinetics; D011110:Polymorphism, Genetic
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D002219:Carbamates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D010880:Piperidines; C503999:SLCO1B1 protein, human; C072379:repaglinide; D000077146:Irinotecan; D002166:Camptothecin