Leukotrienes in ulcerative colitis: results of a multicenter trial of a leukotriene biosynthesis inhibitor, MK-591.
OBJECTIVE
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.
Roberts
W G
WG
Merck Research Laboratories, West Point, Pennsylvania, USA.
Simon
T J
TJ
Berlin
R G
RG
Haggitt
R C
RC
Snyder
E S
ES
Stenson
W F
WF
Hanauer
S B
SB
Reagan
J E
JE
Cagliola
A
A
Tanaka
W K
WK
Simon
S
S
Berger
M L
ML
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*
D007211:Indoles; D016859:Lipoxygenase Inhibitors; D011804:Quinolines; C078266:MK 0591; D007975:Leukotriene B4