Abstract
Effect of ursodeoxycholic acid (UDCA) treatment on the expression and function of intestinal multidrug resistance-associated protein (Mrp) 2 was examined in rats. When rats were orally administered 0.5% UDCA solution for 6 days, mRNA and protein levels of Mrp2 in the intestine were increased about twofold compared with those in untreated rats. In in vitro everted sac study, Mrp2-mediated efflux of 2,4-dinitrophenyl-S-glutathione (DNP-SG) to the mucosal surface was shown to be increased by UDCA treatment. In vivo intestinal exsorption clearance of DNP-SG was also increased by UDCA treatment. In addition, in situ intestinal absorption of methotrexate, a substrate of Mrp2, was decreased by the treatment. These results indicate that the expression and function of intestinal Mrp2 is up-regulated by oral administration of UDCA. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2822–2831, 2009
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