PT  - JOURNAL ARTICLE
AU  - Hiroki Satoh
AU  - Fumiaki Yamashita
AU  - Masayuki Tsujimoto
AU  - Hideyasu Murakami
AU  - Noriko Koyabu
AU  - Hisakazu Ohtani
AU  - Yasufumi Sawada
TI  - CITRUS JUICES INHIBIT THE FUNCTION OF HUMAN ORGANIC ANION-TRANSPORTING POLYPEPTIDE OATP-B
AID  - 10.1124/dmd.104.002337
DP  - 2005 Apr 01
TA  - Drug Metabolism and Disposition
PG  - 518--523
VI  - 33
IP  - 4
4099  - http://dmd.aspetjournals.org/content/33/4/518.short
4100  - http://dmd.aspetjournals.org/content/33/4/518.full
SO  - Drug Metab Dispos2005 Apr 01; 33
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics