5-aminosalicylate therapy

Abstract

Aminosalicylates (5-aminosalicylates, 5-aminosalicylic acid, 5-ASA, mesalamine, mesalazine) are widely used medications as first-line therapy in mild to moderate inflammatory bowel disease, particularly ulcerative colitis [1, 2]. Although the exact mechanism(s) of action remains unclear, they appear to have a number of important anti-inflammatory and immunomodulatory effects. The first drug in this class, sulfasalazine, was originally developed for the treatment of rheumatoid arthritis and is a combination of sulfapyridine, a sulfa antibiotic, and 5-aminosalicylic acid (5-ASA), a compound with anti-inflammatory properties. The discovery of the medication's efficacy in the treatment of inflammatory bowel disease eventually led to elucidation of its pharmacokinetics [3]. The azo bond in the prodrug is cleaved by bacteria in the colon releasing 5-ASA, which has a topical therapeutic effect in the colon, and sulfapyridine, which is absorbed and contributes to the majority of the side effects associated with the drug. What has followed over the past two decades is the development of delivery systems for 5-ASA that allow release in the distal bowel without the potential confounding side effects of the antibiotic. Numerous clinical trials have supported the efficacy of these medications in the treatment of inflammatory bowel disease. Unfortunately there are very few studies in pediatric patients addressing either pharmacokinetic properties or efficacy. Therefore, the gastroenterologist treating children with inflammatory bowel disease must infer best practice from the adult literature [4]. Even in adults, a number of controversies remain in the clinical use of these medications including: the optimum dose and dosing interval for induction and maintenance of remission; the most appropriate preparation given the clinical setting; the overall efficacy in Crohn disease; the efficacy in preventing post-operative recurrence in Crohn disease; chemoprevention for colon cancer; and adherence [5, 6]. © 2008 Springer Science+Business Media, LLC. All rights reserved.