The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced bronchoconstriction in children.

Abstract

To determine the effects of zafirlukast on exercise-induced bronchoconstriction in children. Exercise challenges were done 4 hours after single oral doses of zafirlukast or placebo were administered in asthmatic children (6 to 14 years) treated with beta 2-agonists alone. Subjects randomized to treatment had a >/=20% decrease in forced expiratory volume in 1 second (FEV1 ) after a screening challenge. In a randomized, double-blind, 3-way, crossover design, group 1 (n = 20) received placebo and 5 and 20 mg zafirlukast, and group 2 (n = 19) received placebo and 10 and 40 mg zafirlukast. Maximal percentage fall in FEV1, area under the curve, and time to recovery of FEV1 to within 5% of baseline after the challenge were compared with analysis of variance. Mean values for maximal fall in FEV1 ranged from -8.7% +/- 1.7% to -11.1% +/- 1.9% after zafirlukast compared with -17.1% +/- 1.8% and -16.3% +/- 1.9% after placebo. Differences from placebo for fall in FEV1 and area under the curve were significant (P </=.05) after 5, 20, and 40 mg zafirlukast and approached significance (P </=.08) after 10 mg zafirlukast. After all zafirlukast doses, recovery times (means of 5 to 7 minutes) decreased significantly (P </=.05) and by approximately half compared with placebo (11 and 14 minutes). Safety assessments did not differ among treatments. Four hours after dosing, zafirlukast attenuated exercise-induced bronchoconstriction in children.