title: Effect of BAY x 7195, an oral receptor antagonist of cysteinyl-leukotrienes, on leukotriene D4-induced bronchoconstriction in normal volunteers.
abstract: Leukotrienes (LT) have been proposed to play an important role in the pathogenesis of asthma. This paper reports the results of two studies investigating the effect of BAY x 7195, a new oral receptor antagonist of cysteinyl-leukotrienes, on LTD4-induced bronchoconstriction in healthy male volunteers. Using a double-blind, placebo-controlled, crossover design, volunteers received 250 mg (n = 6; study 1) and 100 and 500 mg (n = 6; study 2) of BAY x 7195. Bronchoprovocation with nebulized LTD4 was performed 2 (250 mg) and 2 and 8 (100 and 500 mg) h p.a. The specific airway's conductance (SGaw) was used to assess the airway's response. Blood samples to determine plasma concentrations of BAY x 7195 were taken at the end of bronchoprovocation. BAY x 7195 showed no effect on baseline lung function. Compared to placebo, the different doses of BAY x 7195 increased the concentration of LTD4 needed to produce a 35% decrease in SGaw 2 h p.a. between 1- and 23-fold. Eight hours p.a., 100 and 500 mg caused shifts in the concentration-response curve of between 1- and 13-fold. There was no predictive relationship between plasma concentrations of BAY x 7195 and the response to LTD4 challenge. However, there was a relationship between dose and effect. No relevant adverse effects were reported. In conclusion, the present results suggest that BAY x 7195 is an effective LTD4-receptor antagonist in man.
authors.affiliation: Institute of Clinical Pharmacology International, Bayer AG, Wuppertal, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wensing
authors.forename: R
authors.initials: R
authors.lastname: Heinig
authors.forename: M
authors.initials: M
authors.lastname: Priesnitz
authors.forename: J
authors.initials: J
authors.lastname: Kuhlmann
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male
chemical_list: D016085:Bronchoconstrictor Agents; D006880:Hydroxy Acids; D017998:Leukotriene D4; C092294:BAY x 7195