This investigation was performed in order to examine the role of sulfidopeptide-
leukotrienes in a chronic
inflammatory bowel disease,
ulcerative colitis, by use of the recently developed
LTD4/
LTE4 antagonist,
SR 2640 (2-[3-(2-quinolylmethoxy)phenylamino]
benzoic acid). Eight
ulcerative colitis patients with a mild to moderate disease activity were included in this open and uncontrolled study and
SR 2640, 250 mg t.i.d., was administered for 6 weeks. Treatment of the patients with
SR 2640 reduced the inhibitory effect of
LTD4 on LTB4-directed chemotaxis of neutrophils purified from their blood. This indicates that the dose administered was sufficiently high to obtain systemic
LTD4 receptor antagonism. Three of the 8 patients were in clinical remission at the end of the study, and the lack of clinical symptoms persisted for at least 2 months after discontinuing the
drug. The condition of 3 patients was unchanged, and that of 2 patients deteriorated after 5 weeks, requiring treatment with
sulphasalazine and
steroids.
SR 2640 was well tolerated by all patients. In a previously published study dealing with 4 weeks
sulphasalazine treatment in the same category of patients, remission rates of 5% and 25% were found in the placebo and
sulphasalazine groups, respectively, and the remission rate of
SR 2640 thus seems to be of the same magnitude as that of
sulphasalazine. The serum and faecal concentrations of
SR 2640, and its metabolite, the beta-
glucuronide, were found to be lower in
ulcerative colitis patients as compared to healthy volunteers, and it is therefore possible that altered pharmacokinetics of
SR 2640 is present in patients with chronic
inflammatory bowel disease.(ABSTRACT TRUNCATED AT 250 WORDS)