Rapid Stimulating Effect of the Antiarrhythmic Agent Amiodarone on Absorption of Organic Anion Compounds
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- SEGAWA Masahiro
- Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University
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- OGURA Jiro
- Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University
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- SEKI Satoru
- Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University
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- ITAGAKI Shirou
- Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University
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- TAKAHASHI Natsuko
- Graduate School of Medicine, Hokkaido University
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- KOBAYASHI Masaki
- Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University
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- HIRANO Takeshi
- Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University
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- YAMAGUCHI Hiroaki
- Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University
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- ISEKI Ken
- Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University
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抄録
In a clinical setting, changes in pharmacokinetics due to drug-drug interactions can often directly affect the therapeutic safety and efficacy of drugs. Recently, interest has been shown in drug-drug interactions in the intestine. It is now recognized that changes in the functions of drug transporters substantially influence the absorption of administered drugs from the intestine. Amiodarone (AMD) is a potent drug used in the treatment of serious supraventricular and ventricular tachyarrhythmias. Despite its potent pharmacological effects, its wide clinical use is precluded by drug-drug interactions. In this study, we characterized the transporter function between AMD and various compounds in human intestinal model Caco-2 cells. AMD significantly and rapidly increased the uptake of [3H]estrone-3-sulfate (E-3-S) for 5 min. The apical-to-basal transport of [3H]E-3-S was significantly increased by AMD. The AMD-stimulated [3H]E-3-S uptake was inhibited by organic anion transporting polypeptide (OATP) substrates. Caco-2 cells treated with AMD showed increased OATP2B1 expression on the cell surface. AMD also increased the absorption of sulfobromophthalein (BSP), which is a typical organic anion compound, and the expression level of Oatp2b1 at the membrane in in vivo experiments. The results indicate that AMD induces OATP2B1/Oatp2b1 expression at the membrane in the intestine and enhances absorption of organic anion compounds.<br>
収録刊行物
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- Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ
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Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 28 (3), 178-186, 2013
日本薬物動態学会
