title: Selective 5-lipoxygenase inhibition in ulcerative colitis.
abstract: Leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) concentrations were measured in rectal dialysis fluid from ten patients with active ulcerative colitis before and after oral administration of 800 mg of the 5-lipoxygenase inhibitor A-64077. The median LTB4 level fell significantly, from 4.9 (range 0.6-20.4) ng/ml before treatment to 1.6 (0.3-5.7) ng/ml after 4 h and 0.7 (0.1-8.0) ng/ml after 8 h; it had returned to pretreatment levels by 28 h. The concentration of PGE2 did not change significantly. The increased generation of 5-lipoxygenase products, such as LTB4, in ulcerative colitis and the potent proinflammatory actions of these products suggest that they have an important role in the amplification of the inflammatory response. A controlled trial to assess the clinical efficacy of A-64077 seems worth while.
authors.affiliation: Department of Medical Gastroenterology, Odense University Hospital, Denmark.
authors.forename: L S
authors.initials: LS
authors.lastname: Laursen
authors.forename: J
authors.initials: J
authors.lastname: Naesdal
authors.forename: K
authors.initials: K
authors.lastname: Bukhave
authors.forename: K
authors.initials: K
authors.lastname: Lauritsen
authors.forename: J
authors.initials: J
authors.lastname: Rask-Madsen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000201:enzymology; D003956:Dialysis; D015232:Dinoprostone / Q000032:analysis*; D004341:Drug Evaluation; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007975:Leukotriene B4 / Q000032:analysis*; D016859:Lipoxygenase Inhibitors; D008875:Middle Aged; D012008:Recurrence; D013997:Time Factors
chemical_list: D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; D001091:Arachidonate Lipoxygenases; D015232:Dinoprostone; C063449:zileuton; D006918:Hydroxyurea