Selective blockade of leukotriene production by a single dose of the FPL 64170XX 0.5% enema in active ulcerative colitis.
Pharmacol Toxicol
; 77(6): 371-6, 1995 Dec.
Article
em En
| MEDLINE
| ID: mdl-8835361
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Colite Ulcerativa
/
Leucotrienos
/
Inibidores de Lipoxigenase
/
Enema
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Aged
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Pharmacol Toxicol
Assunto da revista:
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
1995
Tipo de documento:
Article