INHIBITORY EFFECTS OF BAY X-7195, A CYS LEUKOTRIENE-1 RECEPTOR ANTAGONIST, ON ALLERGEN-INDUCED ASTHMATIC RESPONSES

Background: Leukotriene antagonists may inhibit bronchoconstrictive re sponses to a variety of stimuli. Objective: To evaluate the efficacy a nd safety of a new CYS LT1 antagonist, BAY x 7195, given as a single o ral dose of 500 mg, in prevention of allergen-induced asthmatic respon ses. Methods: This is a randomized, double-blind crossover, placebo-co ntrolled study in mildly asthmatic non-smoking subjects (n = 10) , age d 20 to 32 years (mean 24.8). Following an initial baseline allergen c hallenge, the subjects came back for two other challenges separated by at least a 2-week period, during which placebo or BAY x 7195 was admi nistered two hours before allergen inhalation. Allergen challenges wer e preceded and followed by a methacholine inhalation test (24 hours be fore and 30 hours after). Results: For each subject, the same allergen and doses were used throughout the study. In the randomized (intent-t o-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 concentratio ns of methacholine as compared with -1.77 after placebo; however, the change did not achieve statistical significance, P = .08. Conclusion: BAY x 7195 shows suppressive effects on allergen-induced responses, su ggesting that it may be useful in the treatment of asthma.