1. Leukotrienes in ulcerative colitis: results of a multicenter trial of a leukotriene biosynthesis inhibitor, MK-591.
- Author
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Roberts WG, Simon TJ, Berlin RG, Haggitt RC, Snyder ES, Stenson WF, Hanauer SB, Reagan JE, Cagliola A, Tanaka WK, Simon S, and Berger ML
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Colitis, Ulcerative pathology, Double-Blind Method, Female, Humans, Indoles adverse effects, Leukotriene B4 antagonists & inhibitors, Male, Middle Aged, Quinolines adverse effects, Colitis, Ulcerative drug therapy, Indoles therapeutic use, Lipoxygenase Inhibitors therapeutic use, Quinolines therapeutic use
- Abstract
Background & Aims: Leukotrienes (LTs) are believed to be important in the pathogenesis of ulcerative colitis (UC). The aim of this study was to determine whether inhibition of LT biosynthesis with a 5-lipoxygenase inhibitor (MK-591) induces remission in patients with mild to moderate UC., Methods: One hundred eighty-three patients with mild to moderately active UC enrolled in this randomized parallel group, double-blind study. Patients received placebo or MK-591 at a dose of 12.5, 50, or 100 mg twice daily for 8 weeks. A subset of patients underwent rectal dialysis to determine LTB4 concentration., Results: MK-591 reduced LTB4 concentrations in rectal dialysate at the final determination. The median percent of baseline LTB4 concentration for 100 mg taken twice daily was 1.4% (n = 4); for 50 mg taken twice daily, 16.5% (n = 6); for 12.5 mg taken twice daily, 12% (n = 6); and for placebo, 78% (n = 6). There was no correlation between reduction of LTB4 and remission. Patients in remission at week 8 were as follows: placebo, 9 of 44 (20.5%); 100 mg taken twice daily, 11 of 43 (25.6%); 50 mg taken twice daily, 8 of 49 (16.3%); and 12.5 mg taken twice daily, 4 of 47 (8.5%) (P > 0.10)., Conclusions: MK-591 markedly inhibited LT biosynthesis, but it did not differ significantly from placebo in clinical efficacy. Inhibition of LT biosynthesis was not effective as a single therapeutic modality in active UC.
- Published
- 1997
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