The effect of zafirlukast on repetitive exercise-induced bronchoconstriction: the possible role of leukotrienes in exercise-induced refractoriness.
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 beta(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).


CONCLUSIONS
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.
Dessanges
J F
JF
CHU Cochin, AP-HP-Université Paris 5, Paris, France.
Préfaut
C
C
Taytard
A
A
Matran
R
R
Naya
I
I
Compagnon
A
A
Dinh-Xuan
A T
AT
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects*; D015444:Exercise; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010612:Pharyngitis / Q000139:chemically induced; D048448:Phenylcarbamates; D013449:Sulfonamides; D013997:Time Factors; D014105:Tosyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D014581:Urticaria / Q000139:chemically induced
D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; C062735:zafirlukast