Colonic targeting of aminosalicylates for the treatment of ulcerative colitis.
Aminosalicylates (5-aminosalicylic acid) represent drugs of first choice in the treatment of ulcerative colitis. Two different therapeutic approaches have been employed to target the active 5-aminosalicylic acid to its site of action. Either inactive azo-prodrugs (e.g. sulfasalazine, olsalazine, balsalazide) or special galenic formulations have been developed for topical delivery of 5-aminosalicylic acid to the colon. However, as intestinal physiology, the extent of ulcerative colitis as well as drug disposition demonstrate large interindividual differences, acute healing rates (40-80%) and the maintenance of remission are quite variable. Apparently, therapeutic effects depend on local concentrations of 5-aminosalicylic acid in the colonic mucosa whereas systemic drug exposure might be one determinant of side effects. In general, 5-aminosalicylic acid is well tolerated and withdrawal from therapy is rare. Following administration of azo-prodrugs (e.g. olsalazine), lower plasma concentrations and higher delivery into the colon of 5-aminosalicylic acid can be observed in comparison to special galenic formulations of 5-aminosalicylic acid. Whether such changes in drug disposition will affect therapeutic efficacy remains to be proved by clinical data. Consequently, selection of a particular agent should be based primarily on clinical efficacy, profile of adverse effects, patients' acceptance and economic considerations.
Klotz
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Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstrasse 112, D-70376 Stuttgart, Germany. ulrich.klotz@ikp-stuttgart.de
D000284:Administration, Oral; D000285:Administration, Rectal; D000636:Aminosalicylic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000503:physiopathology; D016503:Drug Delivery Systems; D006801:Humans; D007422:Intestines / Q000502:physiology; D015394:Molecular Structure; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs