Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn's disease.

We studied the therapeutic efficacy of sulfasalazine and its metabolites sulfapyridine and 5-aminosalicylic acid in nine patients with Crohn's disease and in 23 patients with ulcerative colitis. In a randomized, controlled trial, we treated 11 patients for six weeks with 1 g of sulfasalazine three times a day, seven patients with 0.5 g of sulfapyridine three times a day, and 14 patients with 0.5 g of 5-aminosalicylic acid suppositories three times a day. The clinical state of the disease was characterized by an activity index, quality of stool, and remission rate. In addition, we monitored plasma levels of sulfapyridine, 5-aminosalicylic acid, and their acetylated metabolites. The initial activity index (mean +/- S.D.) was significantly reduced by sulfasalazine (from 245 +/- 129 to 100 +/- 71; P < 0.001) and by 5-aminosalicylic acid (from 251 +/- 65 to 90 +/- 93; P < 0.0001), but sulfapyridine was without benefit. Stool quality was also improved by sulfasalazine (82 per cent of the cases) and by 5-aminosalicylic acid (79 per cent). The highest remission rate was achieved with 5-aminosalicylic acid (86 per cent), followed by sulfasalazine (64 per cent) and sulfapyridine (14 per cent). Our investigations show that 5-aminosalicylic acid is the active moiety of sulfasalazine and that this effective metabolite may be an alternative to sulfasalazine in inflammatory bowel disease.

[1]  C. Swan,et al.  Prostaglandin synthetase activity in acute ulcerative colitis: effects of treatment with sulphasalazine, codeine phosphate and prednisolone. , 1979, Gut.

[2]  C. Swan,et al.  Determination of prostaglandin synthetase activity in rectal biopsy material and its significance in colonic disease. , 1978, Gut.

[3]  M. Peppercorn,et al.  Drug therapy: Sulfasalazine. , 1975, The New England journal of medicine.

[4]  G. Corazza,et al.  SALICYLATE OTHER THAN 5-AMINOSALICYLIC ACID INEFFECTIVE IN ULCERATIVE COLITIS , 1978, The Lancet.

[5]  J. V. van Rossum,et al.  Influence of intestinal transit time on azo-reduction of salicylazosulphapyridine (Salazopyrin). , 1979, Gut.

[6]  S. Truelove,et al.  AN EXPERIMENT TO DETERMINE THE ACTIVE THERAPEUTIC MOIETY OF SULPHASALAZINE , 1977, The Lancet.

[7]  J. McManus,et al.  Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. , 1973, The New England journal of medicine.

[8]  R. Lewkonia,et al.  Metabolism of salicylazosulfapyridine in healthy subjects and in patients with ulcerative colitis; Effects of colectomy and of phenobarbital , 1973, Clinical pharmacology and therapeutics.

[9]  U. Zor,et al.  Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine. , 1978, Gastroenterology.

[10]  J. V. Tongeren,et al.  ACTIVE THERAPEUTIC MOIETY OF SULPHASALAZINE , 1978, The Lancet.

[11]  U. Klotz,et al.  Is plasma level monitoring of sulfasalazine indicated in the treatment of Crohn's disease or ulcerative colitis? , 1980, Therapeutic drug monitoring.

[12]  S. Gould.  Assay of prostaglandin-like substances in faeces and their measurement in ulcerative colitis. , 1976, Prostaglandins.

[13]  M. Peppercorn,et al.  Distribution studies of salicylazosulfapyridine and its metabolites. , 1973, Gastroenterology.

[14]  M. Eastwood,et al.  Further studies of sulphasalazine metabolism in the treatment of ulcerative colitis. , 1977, British medical journal.

[15]  D. Evans,et al.  HUMAN ACETYLATION POLYMORPHISM. , 1964, The Journal of laboratory and clinical medicine.

[16]  O. Stendahl,et al.  The effect of sulfasalazine and its active components on human polymorphonuclear leukocyte function in relation to ulcerative colitis. , 2009, Acta medica Scandinavica.

[17]  K. Das,et al.  Clinical Pharmacokinetics of Sulphasalazine , 1976, Clinical pharmacokinetics.

[18]  H. Schröder,et al.  Absorption, metabolism, and excretion of salicylazosulfapyridine in man , 1972, Clinical pharmacology and therapeutics.

[19]  F Kern,et al.  Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. , 1976, Gastroenterology.

[20]  P. Moore,et al.  EFFECTS OF SULPHASALAZINE AND ITS METABOLITES ON PROSTAGLANDIN SYNTHESIS, INACTIVATION AND ACTIONS ON SMOOTH MUSCLE , 1980, British journal of pharmacology.

[21]  J. McManus,et al.  The metabolism of salicylazosulphapyridine in ulcerative colitis , 1973, Gut.