Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake.
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Konig J, Glaeser H, Keiser M, Mandery K, Klotz U, Fromm MF
Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake.
Drug Metab Dispos. 2011 Jun;39(6):1097-102. doi: 10.1124/dmd.110.034991. Epub 2011 Mar 23.
- PubMed ID
- 21430235 [ View in PubMed]
- Abstract
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 K(m) value for mesalazine uptake from 55.1 to 16.3, 24.3, and 32.4 muM, respectively, and the respective V(max) 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.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Mesalazine Solute carrier organic anion transporter family member 1B1 Protein Humans NoSubstrateDetails Mesalazine Solute carrier organic anion transporter family member 1B3 Protein Humans NoSubstrateDetails Mesalazine Solute carrier organic anion transporter family member 2B1 Protein Humans UnknownSubstrateDetails