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 x min-1 for zafirlukast 80 mg compared to 40 L x min-1 for placebo (p=0.004). The corresponding median value for zafirlukast 20 mg was 59.9 L x 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.
Richter
K
K
Krankenhaus Grosshansdorf, Zentrum für Pneumologie und Thoraxchirurgie, Landesversicherungsanstalt Freie und Hansestadt Hamburg, Germany.
Jörres
R A
RA
Magnussen
H
H
D000280:Administration, Inhalation; D000328:Adult; D000388:Air; D000704:Analysis of Variance; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D003080:Cold Temperature; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates; D011336:Probability; D012129:Respiratory Function Tests; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000008:administration & dosage*; D016896:Treatment Outcome
D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; C062735:zafirlukast