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

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)518-523
Number of pages6
JournalDrug Metabolism and Disposition
Volume33
Issue number4
DOIs
Publication statusPublished - 2005 Apr
Externally publishedYes

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Citrus
Glyburide
Anions
Citrus paradisi
Peptides
Intestinal Absorption
Substrates
Hypoglycemic Agents
Pharmaceutical Preparations
Buffers
Epithelial Cells
estrone sulfate
Kidney
Experiments

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. / Satoh, Hiroki; Yamashita, Fumiaki; Tsujimoto, Masayuki; Murakami, Hideyasu; Koyabu, Noriko; Ohtani, Hisakazu; Sawada, Yasufumi.

In: Drug Metabolism and Disposition, Vol. 33, No. 4, 04.2005, p. 518-523.

Research output: Contribution to journalArticle

Satoh, H, Yamashita, F, Tsujimoto, M, Murakami, H, Koyabu, N, Ohtani, H & Sawada, Y 2005, 'Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B', Drug Metabolism and Disposition, vol. 33, no. 4, pp. 518-523. https://doi.org/10.1124/dmd.104.002337
Satoh, Hiroki ; Yamashita, Fumiaki ; Tsujimoto, Masayuki ; Murakami, Hideyasu ; Koyabu, Noriko ; Ohtani, Hisakazu ; Sawada, Yasufumi. / Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. In: Drug Metabolism and Disposition. 2005 ; Vol. 33, No. 4. pp. 518-523.
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