Inhibitory effects of BAY x 7195, a CYS leukotriene 1 receptor antagonist, on allergen-induced asthmatic responses.
BACKGROUND
Leukotriene antagonists may inhibit bronchoconstrictive responses to a variety of stimuli.


OBJECTIVE
To evaluate the efficacy and safety of a new CYS LTI antagonist, BAY x 7195, given as a single oral dose of 500 mg, in prevention of allergen-induced asthmatic responses.


METHODS
This is a randomized, double-blind crossover, placebo-controlled study in mildly asthmatic non-smoking subjects (n = 10), aged 20 to 32 years (mean 24.8). Following an initial baseline allergen challenge, the subjects came back for two other challenges separated by at least a 2-week period, during which placebo or BAY x 7195 was administered two hours before allergen inhalation. Allergen challenges were preceded and followed by a methacholine inhalation test (24 hours before and 30 hours after).


RESULTS
For each subject, the same allergen and doses were used throughout the study. In the randomized (intent-to-treat) population (n = 10), after BAY x 7195, the allergen induced % fall in FEV1 was less than after placebo, with mean between-treatment differences of 31.8 +/- 18.0% during the early asthmatic response, P = .03, and of 54.4 +/- 23.2% during the late asthmatic response (P = .04). The allergen-induced increase in methacholine responsiveness was reduced after BAY x 7195, with a change of -0.45 doubling concentrations of methacholine as compared with -1.77 after placebo; however, the change did not achieve statistical significance, P = .08.


CONCLUSIONS
BAY x 7195 shows suppressive effects on allergen-induced responses, suggesting that it may be useful in the treatment of asthma.
Boulet
L P
LP
Unité de Recherche, Centre de Pneumologie de l'Hôpital Laval, Université Laval, Sainte-Foy, Québec, Canada.
Turcotte
H
H
Laviolette
M
M
Côté
J
J
Wyile
G
G
Bologa
M
M
D000328:Adult; D000485:Allergens / Q000009:adverse effects*; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology* / Q000592:standards / Q000627:therapeutic use; D020024:Leukotriene Antagonists; D008297:Male
D000485:Allergens; D001993:Bronchodilator Agents; D006880:Hydroxy Acids; D020024:Leukotriene Antagonists; C092294:BAY x 7195