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: J Kjeldsen, L S Laursen, J Hillingsø, A Mertz-Nielsen, K Bukhave, J Rask-Madsen, K Lauritsen
• Journal: Pharmacology & toxicology (Pharmacol Toxicol) Vol. 77 Issue 6 Pg. 371-6 (Dec 1995) ISSN: 0901-9928 [Print] Denmark
• PMID: 8835361 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article)

Chemical References

• Dialysis Solutions
• Leukotrienes
• Lipoxygenase Inhibitors
• Pyrazoles
• FPL 64170XX
• Leukotriene B4
• Dinoprostone

Topics

• Adult
• Aged
• Colitis, Ulcerative (drug therapy)
• Dialysis Solutions (chemistry)
• Dinoprostone (analysis)
• Enema
• Humans
• Leukotriene B4 (analysis)
• Leukotrienes (biosynthesis)
• Lipoxygenase Inhibitors (administration & dosage, chemistry)
• Male
• Middle Aged
• Pyrazoles (administration & dosage)
• Rectum
• Time Factors
• Treatment Outcome