title: Selective blockade of leukotriene production by a single dose of the FPL 64170XX 0.5% enema in active ulcerative colitis.
abstract: 5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response of several inflammatory diseases, including ulcerative colitis. FPL 64170XX is a selective inhibitor of the enzyme 5-lipoxygenase. Concentrations of leukotriene B4 and prostaglanding E2 in rectal dialysis fluid from 23 males with clinically and sigmoidoscopically active, distally located ulcerative colitis were measured by radioimmunoassays in a double-blind, placebo-controlled, parallel design study before and after rectal administration of an enema containing 0.5% of FPL 64170XX. Repeated measures analysis of leukotriene B4, after adjusting for baseline, showed a significant treatment effect (P = 0.0014). The concentration of leukotriene B4 from rectal dialysates in patients receiving the active drug dropped to 15% (95% confidence interval 5-40%) of the placebo level in the second dialysis following administration of FPL 64170XX 0.5%. By contrast, prostaglanding E2 concentrations doubled (P = 0.0068) in patients receiving FPL 64170XX 0.5% with no change in the placebo group. These findings demonstrate that a single dose of FPL 64170XX 0.5% enema selectively blocks the generation of the 5-lipoxygenase product, leukotriene B4, to a mean of 85% in the target tissue of inflammation. Topical administration of this new leukotriene synthesis inhibitor may prove to be a clinically useful approach to the treatment of active, distally located ulcerative colitis.
authors.affiliation: Department of Medical Gastroenterology, S, Odense, University Hospital, Denma
authors.forename: J
authors.initials: J
authors.lastname: Kjeldsen
authors.forename: L S
authors.initials: LS
authors.lastname: Laursen
authors.forename: J
authors.initials: J
authors.lastname: Hillingsø
authors.forename: A
authors.initials: A
authors.lastname: Mertz-Nielsen
authors.forename: K
authors.initials: K
authors.lastname: Bukhave
authors.forename: J
authors.initials: J
authors.lastname: Rask-Madsen
authors.forename: K
authors.initials: K
authors.lastname: Lauritsen
mesh_terms: D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D015314:Dialysis Solutions / Q000737:chemistry; D015232:Dinoprostone / Q000032:analysis; D004733:Enema; D006801:Humans; D007975:Leukotriene B4 / Q000032:analysis; D015289:Leukotrienes / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage*; D012007:Rectum; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015314:Dialysis Solutions; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; C103099:FPL 64170XX; D007975:Leukotriene B4; D015232:Dinoprostone