Disease relevance of mesalamine

• Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study [1].
• A comparison of budesonide and mesalamine for active Crohn's disease. International Budesonide-Mesalamine Study Group [2].
• Having found previously that treatment with transdermal nicotine patches and mesalamine (5-aminosalicylic acid) has a beneficial effect on active colitis, we examined the value of transdermal nicotine for the maintenance of remission [3].
• Topical administration of 5-aminosalicylic acid: a therapeutic proposal for the treatment of pouchitis [4].
• Diarrhea associated with mesalamine in a patient with chronic nongranulomatous enterocolitis [5].

Psychiatry related information on mesalamine

• Compared with patients given mesalamine enemas or mesalamine tablets, combination-therapy patients reported an absence of blood in stools significantly sooner and, at all visits, the combination therapy group had the highest percentage of patients who reported no blood in their stools [6].
• CONCLUSIONS: The mesalazine micropellet formulation is as effective as tablets in patients with mild-to-moderate ulcerative colitis, enabling a larger dose to be taken comfortably and conveniently, thereby potentially improving patient compliance, treatment response and quality of life [7].
• Ropivacaine improved mucosal healing and restored colonic motor activity in experimental colitis, similar to budesonide but superior to 5-aminosalicylic acid [8].

High impact information on mesalamine

• We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both [2].
• Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator-activated receptor-gamma [9].
• 5-aminosalicylic acid (5-ASA) is an antiinflammatory drug widely used in the treatment of inflammatory bowel diseases [9].
• Sulfasalazine and its salicylate moiety 5-aminosalicylic acid are among the most effective agents for treating inflammatory bowel disease and rheumatoid arthritis [10].
• Different sensitivity of lamina propria T-cell subsets to nitric oxide-induced apoptosis explains immunomodulatory activity of a nitric oxide-releasing derivative of mesalamine in rodent colitis [11].

Chemical compound and disease context of mesalamine

• In rats treated with 5-aminosalicylic acid, but not in those treated with sulfapyridine, the leakage of 51Cr-labeled red blood cells and the area of gross mucosal lesions after ischemia/reperfusion were significantly reduced as compared with untreated (control) rats [12].
• We have compared the efficacy and tolerability of two such agents, olsalazine and mesalazine, in maintenance therapy of ulcerative colitis [13].
• Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. The Abacus Investigator Group [14].
• When we treated the monolayers with drugs commonly used for the treatment of inflammatory bowel disease, including prednisolone, 5-aminosalicylic acid, metronidazole, and 6-mercaptopurine, we were not able to demonstrate a reduction in carrageenan-induced cell injury; however, catalase at 1 mg/ml decreased carrageenan cytotoxicity [15].
• Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease [16].

Biological context of mesalamine

• From our results we believe that presystemic acetylation of 5-aminosalicylic acid may be mainly mediated by a colonic mucosal enzyme and only to a small extent by fecal (bacterial) processes [17].
• 5-aminosalicylic acid in a slow-release preparation: bioavailability, plasma level, and excretion in humans [18].
• CONCLUSIONS: The beneficial effects of mesalamine in the treatment of inflammatory bowel disease may involve an attenuation of PN-induced cell injury and apoptosis through direct and indirect mechanisms without affecting NO levels [19].
• The release pattern, bioavailability, and kinetics of a 5-aminosalicylic acid tablet with sustained release were studied in humans [18].
• RESULTS: Mesalamine resulted in a dose-dependent decrease in PN-induced apoptosis, whether mesalamine was administered before (>10 micromol/L; IC50, 16 micromol/L), simultaneously (25-200 micromol/L; IC50, 24 micromol/L), or 30 minutes (200 micromol/L) after PN exposure [19].

Anatomical context of mesalamine

• CONCLUSIONS: In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine [2].
• We conclude, therefore, that oral azodisalicylate is a highly effective means of delivery of 5-aminosalicylic acid to the colonic mucosa [20].
• Peroxynitrite-induced apoptosis in human intestinal epithelial cells is attenuated by mesalamine [19].
• Delivery and fate of oral mesalamine microgranules within the human small intestine [21].
• In addition, 5-aminosalicylic acid, which is used for the treatment of intestinal inflammation in inflammatory bowel disease, inhibits the expression of cell-surface activation antigens on mitogen-activated peripheral blood lymphocytes in a dose-dependent manner [22].

Associations of mesalamine with other chemical compounds

• Life-table analysis showed ongoing remission after 6 and 12 mo for Pentasa to be 63% (26 of 41) and 54% (22 of 41) and for Salazopyrin 72% (22 of 31) and 46% (14 of 31) [23].
• Sulfasalazine inhibited pokeweed mitogen-stimulated lymphocyte proliferation, while 5-aminosalicylic acid and sulfapyridine exhibited minimal inhibition [24].
• RESULTS: After 24 months, the risk of clinical relapse was comparable in the azathioprine and mesalamine groups, both on intention-to-treat (odds ratio [OR], 2.04; 95% confidence interval [CI], 0.89-4.67) and per-protocol analyses (OR, 1.79; 95% CI, 0.80-3.97) [16].
• For 4 hours, mean luminal mesalamine and acetyl mesalamine concentrations were 52 and 38 micrograms/mL (duodenum), 59 and 82 micrograms/mL (jejunum), and 64 and 104 micrograms/mL (ileum) [21].
• Olsalazine is a very effective means of delivery of 5-aminosalicylic acid to the colonic mucosa in active disease [25].

Gene context of mesalamine

• We recently reported that 5-aminosalicylic acid (5-ASA) inhibits TNFalpha-regulated IkappaB degradation and NFkappaB activation [26].
• Rapid acetylation in the intestinal wall and liver (t1/2beta 0.5 to 2 hours) and transport probably by P-glycoprotein affect mucosal concentrations of mesalazine, which apparently determine clinical response [27].
• For the substrates tested in this study, mouse Nat3 exhibited activity only toward 5-aminosalicylic acid and only at 1/20 the activity shown by Nat2 [28].
• In the present study, we investigated the effect of sulphasalazine and two related compounds - sulphapyridine and 5-aminosalicylic acid - on M phi activation induced by bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) [29].
• By contrast, 5-aminosalicylic acid induced a threefold increase in the IL-8 release [30].

Analytical, diagnostic and therapeutic context of mesalamine

• We performed a double-blind, multicenter study, comparing MMX mesalamine vs placebo for the treatment of active ulcerative colitis [31].
• Mesalamine in the maintenance treatment of Crohn's disease: a meta-analysis adjusted for confounding variables [32].
• The healing produced by treatment with L651,392 was comparable to that observed after treatment with 5-aminosalicylic acid in a similar manner [33].
• METHODS: A randomized, double-blind study was performed comparing balasalazide, 6.75 g daily, with mesalamine, 2.4 g daily, administered for 4, 8, or 12 weeks to 101 (99 evaluable) patients with symptomatic, sigmoidoscopically verified UC [14].
• Eight and 48 h later, respectively, 58% and 65% of the dose was recovered in the ileostomy effluents, either as 5-aminosalicylic acid still retained in the preparation, free 5-aminosalicylic acid or acetyl-5-aminosalicylic acid [18].

References