The effect of RP 59227, a platelet-activating factor antagonist, against antigen challenge and eosinophil and neutrophil chemotaxis in asthmatics

Platelet-activating factor (PAF), an inflammatory mediator, induces microvascular leak, eosinophil chemotaxis, and possibly increases non-specific bronchial hyperresponsiveness in humans. PAF antagonists may have clinical benefits in asthma. We determined the safety and efficacy of a 240 mg oral dos...

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Bibliographic Details
Published inJournal of lipid mediators and cell signalling Vol. 10; no. 3; p. 345
Main Authors Townley, R G, Eda, R, Hopp, R J, Bewtra, A K, Gillen, M S
Format Journal Article
LanguageEnglish
Published Netherlands 01.09.1994
Subjects
Administration, Oral
Adult
Antigens - immunology
Asthma - blood
Asthma - drug therapy
Asthma - immunology
Chemotaxis, Leukocyte - drug effects
Cross-Over Studies
Double-Blind Method
Eosinophils - drug effects
Eosinophils - immunology
Humans
Male
Neutrophils - drug effects
Neutrophils - immunology
Platelet Activating Factor - antagonists & inhibitors
Pyridines - therapeutic use
Skin Tests
Thiazoles - therapeutic use
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Summary:Platelet-activating factor (PAF), an inflammatory mediator, induces microvascular leak, eosinophil chemotaxis, and possibly increases non-specific bronchial hyperresponsiveness in humans. PAF antagonists may have clinical benefits in asthma. We determined the safety and efficacy of a 240 mg oral dose of RP-59227 in attenuating the early and late phase antigen challenge in eight asthmatics, using a double-blind, placebo-controlled, crossover design. Also determined was the effect of the ex vivo addition of PAF following placebo or drug and the level of neutrophil (NCA) and eosinophil chemotactic activity (ECA) in the serum immediately, and 4 h after antigen challenge with either drug or placebo. There was not a significant difference in the maximum percent fall in FEV1 during the early and late phase on screening or placebo days or drug RP-59227 days. There was a significant inhibitory effect (p < 0.05) in peak ECA and NCA in blood after RP-59227. The addition of PAF to ex vivo serum was less effective in inducing chemotaxis to eosinophils following RP-59227 (p < 0.05). RP-59227 attenuated the release of NCA and ECA after antigen challenge, and reduced the effect of exogenously added PAF in inducing eosinophil chemotaxis but did not protect against the antigen-induced early or late phase response.
ISSN:0929-7855