Forskning ved Københavns Universitet - Københavns Universitet

Forside

Effect of the leukotriene LTD4/LTE4 antagonist, SR 2640, in ulcerative colitis: an open clinical study

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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)

OriginalsprogEngelsk
TidsskriftProstaglandins, Leukotrienes & Essential Fatty Acids
Vol/bind42
Udgave nummer3
Sider (fra-til)181-4
Antal sider4
ISSN0952-3278
StatusUdgivet - mar. 1991

ID: 218727820