Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B

Hiroki Satoh, Fumiaki Yamashita, Masayuki Tsujimoto, Hideyasu Murakami, Noriko Koyabu, Hisakazu Ohtani, Yasufumi Sawada

研究成果: Article

186 引用 (Scopus)

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Human organic anion-transporting polypeptide B (OATP-B; OATP2B1) is expressed in the human intestinal epithelial cells, and is suggested to be involved in the intestinal absorption of anionic drugs in vivo. Although citrus juices have been shown to inhibit the function of human OATP-A (OATP1A2), the effect of citrus juices on the OATP-B function remains unclear. In this study, we aimed to examine the effects of citrus juices on the function of OATP-B. The effects of citrus juices on the uptake of estrone-3-sulfate, a typical substrate for OATP-B, into human embryonic kidney 293 cells stably expressing OATP-B were evaluated. Juices were diluted with uptake buffer, adjusted to pH 7.4 and approximately 300 mOsm, and used for the experiments. Grapefruit juice (GFJ) and orange juice (OJ) at a concentration of 5% significantly inhibited the OATP-B-mediated uptake of estrone-3-sulfate by 82 and 53%, respectively. Major constituents of GFJ and OJ also significantly inhibited the OATP-B-mediated uptake of estrone-3-sulfate. Glibenclamide, a hypoglycemic drug, was identified for the first time as a substrate for OATP-B with a Kt value of 6.26 μM. GFJ and OJ inhibited the OATP-B-mediated uptake of glibenclamide. These results suggest that citrus juices may inhibit the intestinal absorption of anionic drugs, such as glibenclamide, via the inhibition of OATP-B.

元の言語English
ページ(範囲)518-523
ページ数6
ジャーナルDrug Metabolism and Disposition
33
発行部数4
DOI
出版物ステータスPublished - 2005 4 1
外部発表Yes

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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