TY - JOUR T1 - Role of Organic Anion-Transporting Polypeptides for Cellular Mesalazine (5-Aminosalicylic Acid) Uptake JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1097 LP - 1102 DO - 10.1124/dmd.110.034991 VL - 39 IS - 6 AU - Jörg König AU - Hartmut Glaeser AU - Markus Keiser AU - Kathrin Mandery AU - Ulrich Klotz AU - Martin F. Fromm Y1 - 2011/06/01 UR - http://dmd.aspetjournals.org/content/39/6/1097.abstract N2 - The therapeutic effects and metabolism of mesalazine (5-aminosalicylic acid) in patients with inflammatory bowel disease require intracellular accumulation of the drug in intestinal epithelial cells and hepatocytes. The molecular mechanisms of mesalazine uptake into cells have not been characterized so far. Using human embryonic kidney cells stably expressing uptake transporters of the organic anion-transporting polypeptide (OATP) family, which are expressed in human intestine and/or liver, we found that mesalazine uptake is mediated by OATP1B1, OATP1B3, and OATP2B1 but not by OATP1A2 and OATP4A1. Moreover, genetic variations (*1b, *5, *15) in the SLCO1B1 gene encoding OATP1B1 reduced the Km value for mesalazine uptake from 55.1 to 16.3, 24.3, and 32.4 μM, respectively, and the respective Vmax values. Finally, budesonide, cyclosporine, and rifampin were identified as inhibitors of OATP1B1-, OATP1B3-, and OATP2B1-meditated mesalazine uptake. These in vitro data indicate that OATP-mediated uptake and its modification by genetic factors and comedications may play a role for mesalazine effects. ER -