Effect of the oral leukotriene antagonist, ICI 204,219, on antigen-induced bronchoconstriction in subjects with asthma

Abstract We studied the effect of a single oral dose of ICI 204,219 on subject response to bronchoprovocation and quantitative skin testing with standardized allergen (cat dander). Cat-allergic male subjects with asthma entered the double-blind, randomized, placebo-controlled, crossover study. Each subject received a 40 mg dose of ICI 204,219 or placebo on study days separated by at least 10 days. After dosing, each subject underwent bronchoprovocation with cat allergen until a provocative dose of allergen caused a 20% decrease in FEV 1 or a maximum dose of 30,000 AU/ml was reached. Fifteen subjects entered and 13 completed the study. No significant shift in the dose-response curve of the quantitative skin test occurred in any subject. A mean tenfold increase in the interpolated provocative concentration causing a 20% decrease in FEV 1 was observed between ICI 204,219 (6996 ± 3204 AU/ml) and placebo (460 ± 98 AU/ml). Eight of 12 subjects required more antigen to provoke a bronchoprovocation response after dosing with ICI 204,219 than that required with placebo (range, threefold to 30-fold), three demonstrated no difference (less than twofold), and one subject required less antigen after ICI 204,219 (sevenfold less). Area under the curve measurements were significantly different ( p