Effects of a thromboxane-receptor antagonist, BAY u 3405, on prostaglandin D2- and exercise-induced bronchoconstriction

• Published in: Journal of allergy and clinical immunology Vol. 89; no. 6; p. 1119
• Main Authors: Magnussen, H, Boerger, S, Templin, K, Baunack, A R
• Format: Journal Article
• Language: English
• Published: United States 01-06-1992
• Subjects: Air; Airway Resistance - drug effects; Asthma, Exercise-Induced - drug therapy; Asthma, Exercise-Induced - physiopathology; Bronchial Provocation Tests - methods; Bronchoconstriction - drug effects; Carbazoles - adverse effects; Carbazoles - therapeutic use; Cold Temperature; Dose-Response Relationship, Drug; Double-Blind Method; Drug Evaluation; Forced Expiratory Volume - drug effects; Humans; Male; Prostaglandin D2 - administration & dosage; Prostaglandin D2 - adverse effects; Receptors, Prostaglandin - drug effects; Receptors, Thromboxane; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Thromboxanes - antagonists & inhibitors; Time Factors
• ISSN: 0091-6749
• DOI: 10.1016/0091-6749(92)90295-D

In the pathogenesis of exercise-induced bronchoconstriction (EIB), prostaglandin D2 (PGD2) may play a role as a newly generated, mast cell-derived mediator. As the bronchoconstrictor effects of PGD2 are predominantly mediated via stimulation of thromboxane receptors in the lung, we studied a novel, orally effective, thromboxane-receptor antagonist, BAY u 3405, on EIB in 12 male subjects with mild asthma. On 4 study days, we determined, in a randomized, double-blind, placebo-controlled, crossover fashion, the effects of 20 mg of BAY u 3405 administered orally 1 hour before PGD2 and exercise challenges, respectively. Increasing dosages of PGD2 were inhaled to establish dose-response curves that allowed determination of the provocative concentration necessary to decrease FEV1 by at least 20% (PC20) and to increase specific airway resistance (SR(aw)) by 100% (PC100). EIB was measured as a maximal fall/increase in postexertional FEV1/SR(aw) after bicycle exercise and cold-air breathing. Prechallenge lung-function values were similar on all four occasions. BAY u 3405 did not elicit any effect on resting bronchial tone. After placebo, the geometric means (SD) of PC20 and PC100 were 0.0380 (2.6) and 0.0266 (2.4) mg/ml, increasing to 0.554 (5.9) and 0.143 (8.1) mg/ml after BAY u 3405 (p = 0.0002). Mean (SD) maximal postexertional decrease in FEV1 and increase in SR(aw) after placebo was 29.4% (16.4%) and 280% (135%), and after BAY u 3405, 31.4% (18.1%) and 379% (281%) (not significant). No clinically relevant BAY u 3405-related side effects were observed. From these results we conclude that BAY u 3405 is highly effective in attenuating PGD2-induced bronchoconstriction.