EFFECT OF BAY-X-7195, AN ORAL RECEPTOR ANTAGONIST OF CYSTEINYL-LEUKOTRIENES, ON LEUKOTRIENE-D-4 INDUCED BRONCHOCONSTRICTION IN NORMAL VOLUNTEERS

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 LTD(4)-induced bronchoconstriction in h ealthy male volunteers. Using a double-blind, placebo-controlled, cros sover design, volunteers received 250 mg (n = 6; study 1) and 100 and 500 mg (n = 6; study 2) of BAY x 7195. Bronchoprovocation with nebuliz ed LTD, 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 n o effect on baseline lung function. Compared to placebo, the different doses of BAY x 7195 increased the concentration of LTD(4) needed to p roduce 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-respons e curve of between 1- and 13-fold. There was no predictive relationshi p between plasma concentrations of BAY x 7195 and the response to LTD( 4) challenge. However, there was a relationship between dose and effec t. No relevant adverse effects were reported. In conclusion, the prese nt results suggest that BAY x 7195 is an effective LTD(4)-receptor ant agonist in man.