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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Townley
R G
RG
Allergic Disease Center, Creighton University, Omaha, NE 68178.
Eda
R
R
Hopp
R J
RJ
Bewtra
A K
AK
Gillen
M S
MS
D000284:Administration, Oral; D000328:Adult; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000627:therapeutic use*; D012882:Skin Tests; D013844:Thiazoles / Q000627:therapeutic use*
D000941:Antigens; D010972:Platelet Activating Factor; D011725:Pyridines; D013844:Thiazoles; C065022:RP 59227