The effect of zafirlukast on repetitive exercise–induced bronchoconstriction: The possible role of leukotrienes in exercise-induced refractoriness

• Published in: Journal of allergy and clinical immunology 1999-12, Vol.104 (6), p.1155-1161
• Main Authors: Dessanges, Jean-François, Préfaut, Christian, Taytard, André, Matran, Régis, Naya, Ian, Compagnon, Anne, Dinh-Xuan, A.Tuan
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Area Under Curve; Asthma - drug therapy; Asthma - physiopathology; Biological and medical sciences; Bronchoconstriction - drug effects; Exercise; Exercise-induced asthma; exercise-induced refractoriness; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists - therapeutic use; leukotriene-receptor antagonists; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pharyngitis - chemically induced; Respiratory system; Time Factors; Tosyl Compounds - adverse effects; Tosyl Compounds - therapeutic use; Urticaria - chemically induced; zafirlukast
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/S0091-6749(99)70007-2

Background: Single doses of zafirlukast attenuate exercise-induced bronchoconstriction (EIB), but previous studies have not measured zafirlukast’s effects after regular dosing or its duration of effect beyond 4 hours. Objective: The purpose of this study was to assess the effects of zafirlukast 20 mg and 80 mg twice daily compared with placebo on exercise challenges performed at 2 and 8 hours after the last dose of regular administration. Methods: Twenty-four adult patients with stable asthma taking β 2-agonists, inhaled corticosteroids, or both received treatment with zafirlukast (20 mg and 80 mg) and placebo. The patients were treated twice daily for 14 days in a randomized, double-blind, 3-way cross-over fashion, with a 7-day washout period between each treatment. Exercise challenges were performed at 2 and 8 hours after the morning dose on day 14. FEV 1 was measured before exercise and at set intervals after exercise until it returned to within 7% of its baseline value. Results: Both zafirlukast treatments significantly reduced EIB, as measured by the area under the FEV 1 time curve after the 2-hour ( P < .001) and 8-hour ( P < .001) exercise challenges and maximum fall in FEV 1 at the 2-hour challenge ( P < .001). The comparison at 8 hours between treatments was affected by the unexpected finding that EIB was less in the placebo group after the 8-hour challenge than after the 2-hour challenge, as measured by the within-group change in the maximum fall in FEV 1 ( P < .001) and the area under the FEV 1 time curve ( P = .0023). Conclusion: Regular zafirlukast treatment protects against EIB for at least 8 hours after regular dosing. A refractory period, which may be caused by exercise-induced leukotriene release, may last for up to 6 hours after the initial response to exercise. (J Allergy Clin Immunol 1999;1155-61.)