This study is a double-blind controlled trial in 86 patients of the efficacy of retention enemas containing 4 g 5-aminosalicylic acid (5-ASA), believed to be the active metabolite of sulphasalazine, compared with retention enemas of 100 mg of hydrocortisone for the topical treatment of mild or moderate ulcerative colitis. 5-ASA enemas given to 44 patients were significantly more effective than hydrocortisone enemas given to 42 patients, and produced 93, 93, and 77% remission in clinical, sigmoidoscopic, and histological terms, respectively, compared with corresponding remission rates of 57, 54, and 33% in the hydrocortisone treated patients.
"Data from clinical trials show that topical 5-ASA therapy is superior to oral therapy in distal UC and is an important part of the therapy in more extensive forms of UC up to pancolitis and is therefore recommended in current international guidelines.4,6,27,28 Topical use of 5-ASA was first described in 1981.26 Dr Falk Pharma’s (Freiburg, Germany) 250 mg Salofalk® suppositories launched in March 1984 were the first pure 5-ASA preparation worldwide. "
[Show abstract][Hide abstract] ABSTRACT: In 1977, 5-aminosalicylic acid (5-ASA) was discovered as a therapeutically active moiety of sulfasalazine (SASP) and was launched for topical and oral therapy of ulcerative colitis (UC) in 1984. As a first-step, delivery systems had to be developed to protect 5-ASA against absorption in the upper gastrointestinal tract, resulting in different and competing strategies (azo compounds, controlled release, and pH-dependent release). In a second step, at the beginning of the new century, coinciding with the expiration of patent protection for the first 5-ASA formulations, two component composite release mechanisms (pH-dependent and controlled release) were developed. Furthermore, the drug was formulated as granules instead of tablets, allowing higher unit strengths compared with tablets. Neither Salofalk Granu-Stix®, nor MMX 5-ASA, nor Pentasa® granules have initially been developed for once-daily (OD) dosing. A review of the achievements of 20 years of 5-ASA development has demonstrated that 5-ASA has equal efficacy compared with SASP at best, that there are no measurable differences in efficacy between various 5-ASA preparations, and that in a group of patients tolerating SASP, adverse event profiles of SASP and 5-ASA did not differ significantly, with SASP being the far cheaper substance. Therefore, drug adherence came into focus as a new goal for improving UC therapy. Although adherence is a complex and multifactorial construct, a simple dosing schedule may contribute to higher drug adherence and better efficacy of treatment. Simultaneously, the US 5-ASA market, estimated to be worth US$1.4 billion, is expected to grow continuously. Naturally, this very competitive market is not only driven by scientific progress but also by commercial interests. Thus, patents for minor changes to the formulation may serve as protection against drug companies trying to launch generic versions. Randomized controlled trials performed on OD dosing in induction of remission have demonstrated that OD administration of 5-ASA is as effective as conventional dosing in mild to moderate active UC. The three 5-ASA products MMX, Salofalk®, and Pentasa® employed in those studies so far have not shown differences in efficacy between OD and conventional dosing. No differences regarding safety outcomes have been detected between OD and conventional dosing, including incidence of adverse events, serious adverse events, or withdrawal from treatment due to an adverse event. Although the majority of patients prefer OD dosing to conventional dosing, it was not possible to detect differences in adherence between OD and multiple dose regimens in the clinical trial setting. Well-designed and controlled large-scale community-based studies are necessary to further investigate and prove the point of improved long-term adherence and treatment efficacy in OD dosing.
Clinical and Experimental Gastroenterology 09/2014; 2014: 7:369 - 383. DOI:10.2147/CEG.S35691
"For more than 6 decades, the active metabolite, 5- ASA, has been administered in the form of the pro-drug SASP. 5-ASA was found to inhibit leukocyte motility which suggested its efficacy in UC  and the first report for a trial in patients with UC was published in the early eighties . Since then manifold 5-ASA based formulations and delivery systems were constantly developed and improved. "
[Show abstract][Hide abstract] ABSTRACT: Aminosalicylates are the most common drugs for the primary treatment of inflammatory bowel disease. Various pro-drugs and formulations were developed in order to improve pharmacological profiles, optimize bioavailability and to gain highest efficacy in the treatment of ulcerative colitis (UC) and Crohn's disease. In vitro studies have greatly contributed to the understanding of the molecular actions in vivo and clinical studies have proven aminosalicylates to be effective and safe. This review summarizes the current knowledge on the molecular, pharmacological and clinical properties of aminosalicylates with respect to chemoprevention for UC-associated colorectal cancer.
Best practice & research. Clinical gastroenterology 08/2011; 25(4-5):535-46. DOI:10.1016/j.bpg.2011.10.013 · 3.48 Impact Factor
"conclusion, the results of the present study suggest a restricted absorption of 5-ASA in the large bowel confirming observations with sulphasalazine. The similar permeability pattern in the different areas of the large bowel may support the assumption that increased efficacy towards colitis engaging the right colon may be achieved by therapeutic regimens providing large amounts of 5-ASA to the lumen there, in line with the results after high dose 5-ASA enema treatment in proctosigmoiditis (Azad Khan et al., 1977; Campieri et al., 1981 "
[Show abstract][Hide abstract] ABSTRACT: In order to clarify the characteristics of absorption of 5-aminosalicylic acid (5-ASA) from the colon, a neutral solution was instilled into the right part of the colon and the rectum, respectively, in six volunteers. A laxative (bisacodyl) and liquid meals were given prior to each instillation. No significant difference could be demonstrated between the two parts of the large bowel, but the absorption was considerably restricted compared with previous results obtained from the jejunum. The results confirm in a direct manner earlier observations on 5-ASA released from sulphasalazine.
British Journal of Clinical Pharmacology 03/1988; 25(2):269-72. DOI:10.1111/j.1365-2125.1988.tb03301.x · 3.88 Impact Factor
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