Salicylates for inflammatory bowel disease

https://doi.org/10.1016/0950-3528(94)90002-7Get rights and content

Abstract

Targeted delivery of 5-aminosalicylic acid to the small intestine and colon by controlled-release or azo-bonded compounds potentially offers treatment for ileal Crohn's disease as well as ulcerative colitis. The pharmacokinetics of sulphasalazine and aminosalicylate derivatives have been discussed and potential modes of action reviewed. These include actions on epithelial cell-surface receptors, cellular events and barrier function. Evidence for an influence of salicylates on circulating and tissue inflammatory cells is presented, as well as actions on adhesion molecules, chemotactic peptides, eicosanoids, cytokines and reactive oxygen metabolites. The precise mechanism remains unknown, but a pluripotential mode of action is an advantage when influencing the network of events that constitutes chronic inflammation. Controlled clinical trials of salicylates in ulcerative colitis and Crohn's disease have been reviewed. Their main role remains as maintenance therapy for ulcerative colitis, but relatively high doses of controlled-release preparations benefit patients with ileal Crohn's disease, following resection, or those who have recently relapsed. Finally, issues of clinical relevance have been addressed, including the choice of salicylate and safety, indications for initiating therapy, dose and duration of treatment, role in managing refractory colitis and future developments.

References (160)

  • BA Lashner et al.

    The effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis: a case control study

    Gastroenterology

    (1989)
  • H Malchow et al.

    European Co-operative Crohn's Disease Study (ECCDS): results of drug treatment

    Gastroenterology

    (1984)
  • S Meyers et al.

    Olsalazine sodium in the treatment of active ulcerative colitis in patients intolerant of sulfasalazine

  • JJ Misiewicz et al.

    Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis

    Lancet

    (1965)
  • CJJ Mulder et al.

    Double-blind comparison of slow-release 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis

    Gastroenterology

    (1988)
  • HJ Pieniaszek et al.

    Capacity-limited gut wall metabolism of 5-aminosalicylic acid, a therapeutically active metabolite of sulfasalazine, in rats

    Journal of Pharmacological Science

    (1979)
  • C Prantera et al.

    Oral 5-aminosalicylic acid (Asacol) in the maintenance treatment of Crohn's disease

    Gastroenterology

    (1992)
  • WE Pullman et al.

    Enhanced mucosal cytokine production in inflammatory bowel disease

    Gastroenterology

    (1992)
  • NA Punchard et al.

    The effects of sulpha-salazine and its metabolites on prostaglandin production by human mononuclear cells

    Biochemical Pharmacology

    (1992)
  • Choosing an oral 5-aminosalicylic acid preparation for ulcerative colitis

    Drug Therapy Bulletin

    (1992)
  • P Anthonisen et al.

    The clinical effect of salazosulphapyridine (Salazopyrin) in Crohn's disease

  • MN Aparicio-Pages et al.

    Inhibition of cell-mediated cytotoxicity by sulphasalazine: effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on in vitro natural killer cell activity

    Gut

    (1990)
  • AK Azad Khan et al.

    An experiment to determine the active therapeutic moiety of sulphasalazine

    Lancet

    (1977)
  • AK Azad Khan et al.

    Optimum dose of SASP for maintenance treatment in ulcerative colitis

    Gut

    (1980)
  • L Bergman et al.

    Post-operative treatment with corticosteroids and salazo-sulphapyridine (Salazopyrin) after radical resection for Crohn's disease

    Scandinavian Journal of Gastroenterology

    (1976)
  • S Bondesen

    Mesalazine (Pentasa) as prophylaxis in Crohn's disease

  • NK Boughton-Smith et al.

    Lipid mediators and cytokines in inflammatory bowel disease

    European Journal of Gastroenterology and Hepatology

    (1990)
  • IC Calder et al.

    Nephrotoxic lesions from 5-aminosalicylic acid

    British Medical Journal

    (1972)
  • M Campieri et al.

    Optimum dosage of 5-ASA aminosalicylic acid as rectal enemas in patients with active ulcerative colitis

    Gut

    (1991)
  • R Caprilli et al.

    5-Aminosalicylic acid in the prevention of Crohn's disease post-operative recurrence

    Gastroenterology

    (1992)
  • C Clerici et al.

    Aminoacid derivatives of 5-ASA as novel prodrugs for colon-specific drug delivery

    Gastroenterology

    (1993)
  • F Cominelli et al.

    Interleukin-1 gene expression, synthesis and effect of specific IL-1 receptor blockade in rabbit immune complex colitis

    Journal of Clinical Investigation

    (1990)
  • F Cominelli et al.

    IL-1 receptor antagonist (IL-IRA) blocks the pro-inflammatory activity of IL-1 produced in the colon during rabbit immune colitis

    Gastroenterology

    (1991)
  • B Crotty et al.

    Drug therapy of ulcerative colitis

    British Journal of Clinical Pharmacology

    (1992)
  • B Crotty et al.

    Salicylates used in inflammatory bowel disease and colchicine impair interferon-γ induced HLA-DR expression

    Gut

    (1992)
  • B Crotty et al.

    Inhibition of binding of interferon-γ to its receptor by salicylates used in inflammatory bowel disease

    Gut

    (1992)
  • F Dallegri et al.

    Cytoprotection against neutrophil derived hypochlorous acid: a potential mechanism for the therapeutic action of 5-aminosalicylic acid in ulcerative colitis

    Gut

    (1990)
  • PS Davies et al.

    Maintenance of remission in ulcerative colitis with sulphasalazine or a high fibre diet: a clinical trial

    British Medical Journal

    (1978)
  • AE Davis et al.

    The effect of therapeutic drugs used in inflammatory bowel disease on the incidence and growth of colonic cancer in the dimethylhydrazine rat model

    British Journal of Cancer

    (1992)
  • MJ Dew et al.

    Maintenance of remission in ulcerative colitis with oral preparation of 5-aminosalicylic acid

    British Medical Journal

    (1982)
  • MJ Dew et al.

    Comparison of the absorption and metabolism of sulphasalazine and acrylic-coated 5-aminosalicylic acid in normal subjects and patients with colitis

    British Journal of Pharmacology

    (1984)
  • AP Dick et al.

    Controlled trial of sulphasalazine in the treatment of ulcerative colitis

    Gut

    (1964)
  • AS Dissanayake et al.

    A controlled therapeutic trial of long-term maintenance treatment of ulcerative colitis with sulphasalazine (Salazopyrin)

    Gut

    (1973)
  • K Ewe et al.

    Treatment of ulcerative colitis with olsalazine and sulphasalazine: efficacy and side-effects

    Scandinavian Journal of Gastroenterology

    (1988)
  • GE Feurle et al.

    Olsalazine versus placebo in the treatment of mild to moderate ulcerative colitis: a randomized double blind trial

    Gut

    (1989)
  • R Fiasse et al.

    Prevention of Crohn's disease recurrence after intestinal resection with Eudragit-L coated 5-aminosalicylic acid

  • WE Fleig et al.

    Prospective, randomized, double-blind comparison of benzalazine and sulfasalazine in the treatment of active ulcerative colitis

    Digestion

    (1988)
  • P Florent et al.

    Placebo-controlled trial of Claversal in the prevention of early endoscopic relapse after curative resection for Crohn's disease

    Gastroenterology

    (1992)
  • P Fockens et al.

    Relapse-prevention of ulcerative colitis: double-blind comparison of 1.5 g v 3 g oral mesalazine (Pentasa)

    Gastroenterology

    (1993)
  • CC Fox et al.

    Modulation of mediator release from human intestinal mast cells by sulfasalazine and 5-aminosalicylic acid

    Digestive Diseases and Sciences

    (1991)
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