Organic Anion Transporting Polypeptide (OATP)1B1 and OATP1B3 as Important Regulators of the Pharmacokinetics of Substrate Drugs

• Maeda Kazuya

  Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, 
The University of Tokyo

抄録

Nobody doubts the importance of organic anion transporting polypeptide (OATP)1B1 and 1B3 in the clinical pharmacokinetics of substrate drugs. Based on the theory of pharmacokinetics, even if a drug is eliminated from the body by extensive metabolism, the rate-determining process of the hepatic intrinsic clearance of OATP substrates is often hepatic uptake. Because of their broad substrate specificities, once the functions of OATP1B1 or OATP1B3 are altered by several kinds of special occasions such as drug–drug interactions (DDI) and genetic polymorphisms of transporter genes, the hepatic clearance of many kinds of structurally-unrelated drugs is expected to be changed. In some cases, these alterations of pharmacokinetics lead to modified pharmacological effects and adverse reactions such as statin-induced myotoxicity and the glucose-lowering effect of anti-diabetes drugs. Thus, appropriate methods with which to quantitatively predict the changes in plasma and tissue concentrations of drugs are needed in the process of drug development. As for DDI, a static model that takes into consideration of the theoretically-maximum unbound inhibitor concentration is often used for the sensitive detection of possible DDI risks and this method has been adopted in several regulatory guidance/guidelines on DDI. Regarding genetic polymorphisms, the effects of SLCO1B1 c.388A>G and c.521T>C on the pharmacokinetics of substrate drugs have been extensively investigated. Even though there are some discrepancies, c.521T>C generally decreased hepatic uptake activity, while c.388A>G tended to slightly increase it. This article briefly summarizes the current status of research on hepatic OATP1B1 and OATP1B3 and the clinical significance of their functions.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 38 (2), 155-168, 2015

  公益社団法人 日本薬学会

キーワード

• organic anion transporting polypeptide
• hepatocyte
• genetic polymorphism
• drug–drug interaction

詳細情報

• CRID: 1390001204633124736
• NII論文ID: 130004872264
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b14-00767
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 026069524
• PubMed: 25747975
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026069524
• Web Site: https://www.jstage.jst.go.jp/article/bpb/38/2/38_b14-00767/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015279163
• 本文言語コード: en
• データソース種別:
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