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

Abstract
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.
AuthorsK Richter, R A Jörres, H Magnussen
JournalThe European respiratory journal (Eur Respir J) Vol. 15 Issue 4 Pg. 693-9 (Apr 2000) ISSN: 0903-1936 [Print] England
PMID10780761 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Indoles
  • Leukotriene Antagonists
  • Phenylcarbamates
  • Sulfonamides
  • Tosyl Compounds
  • zafirlukast
Topics
  • Administration, Inhalation
  • Adult
  • Air
  • Analysis of Variance
  • Asthma (diagnosis, drug therapy, physiopathology)
  • Bronchial Provocation Tests
  • Bronchoconstriction (drug effects)
  • Cold Temperature
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Indoles
  • Leukotriene Antagonists (administration & dosage)
  • Male
  • Middle Aged
  • Phenylcarbamates
  • Probability
  • Respiratory Function Tests
  • Sulfonamides
  • Tosyl Compounds (administration & dosage)
  • Treatment Outcome

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