The Pharmacological Profile and Clinical Use of Mesalazine (5-Aminosalicylic Acid)

For more than 30 years mesalazine (5-aminosalicylic acid; 5-ASA) has been used for the treatment of chronic inflammatory bowel disease (IBD) especially in ulcerative colitis (UC). During this time various rectal and oral formulations have been developed. The modified drug delivery systems were designed to release sufficient 5-ASA at the sites of inflammation. Such a drug targeting strategy is needed for its topical action and especially because local concentrations in the mucosa will determine the clinical outcome. The absorbed part (20–40% of the dose) of 5-ASA is rapidly and presystemically acetylated (t_1/2: 1–2.5 h; CL: 300–690 mL/min). Consequently, the systemic exposure of 5-ASA is low and adverse effects are in the range of placebo treatment. The polypotent 5-ASA has a wide spectrum of pharmacological properties and its exact mode of action is not yet clear. Recent meta-analyses of randomized placebo-controlled clinical trials provide convincing data that 5-ASA is the preferred first-line therapy for the acute treatment of mild-to-moderate UC (NNT:6) and for remission management (NNT:4). There is also some clinical benefit for patients with active Crohn's disease (NNT:7) and in the prevention of postsurgical relapse (NNT:10). There is increasing evidence that 5-ASA also has some therapeutic potential for chemoprevention of colorectal cancer, diverticular disease and irritable bowel syndrome. In all clinical studies, the side effects of 5-ASA were very low (5–10%), mild and comparable to placebo. Thus, its use is very safe and 5-ASA will remain an interesting and valuable agent. It is anticipated that more selective drug targeting, including galenic innovations and an optimized dosaging schedule, could result in some improvement of the wide use of 5-ASA.