Efficacy and duration of action of the antileukotriene zafirlukast on cold air‐induced bronchoconstriction

The objectives of the study were to assess the magnitude of the effect of the leukotriene receptor antagonist, zafirlukast, against cold air‐induced bronchoconstriction following the first dose and to assess magnitude and duration after 5 days of dosing. Nineteen patients with asthma were included. In a randomized cross‐over design, either zafirlukast 20 mg or 80 mg b.d. or placebo were given over 5 days. Challenges were performed 3 h post first dose and 3, 8, 12 and 24 h post last dose. The authors assessed the provocative ventilation rate necessary to achieve a 10% (PV10) and 20% (PV20) fall in forced expiratory volume in one second. The median PV20 3 h post first dose was 69.1 L·min ‐1 for zafirlukast 80 mg compared to 40 L·min ‐1 for placebo (p=0.004). The corresponding median value for zafirlukast 20 mg was 59.9 L·min ‐1 (p=0.06). At steady state the differences in PV20, between zafirlukast 80 mg and placebo were significant at 8 h and 12 h post last dose. The corresponding difference for zafirlukast 20 mg was statistically significant at 8 h post last dose. The analysis of PV10 yielded compatible results. There was no significant protection 24 h after last dose. This study has demonstrated that zafirlukast offers significant protection against cold air‐induced bronchoconstriction in asthma. The degree and duration of protection were dose‐dependent. However, there was a large interindividual variability for the protective effect of this leukotriene receptor antagonist.