Effect of a leukotriene antagonist, ONO-1078, on bronchial hyperresponsiveness in patients with asthma

Respir Med. 1993 Feb;87(2):133-8. doi: 10.1016/0954-6111(93)90141-l.


To evaluate the involvement of sulphidopeptide leukotrienes on bronchial hyperresponsiveness in asthma, we examined the effects of a specific orally active leukotriene antagonist (ONO-1078) on bronchial responsiveness to methacholine in stable asthmatic subjects by a double-blinded, randomized, two-phase crossover study. Eleven asthmatic subjects received ONO-1078 (225 mg twice a day) or placebo. After 1 week administration of ONO-1078 or placebo, the subjects underwent methacholine challenge test. Test drug administrations were then discontinued for 1 week, and the subjects were then crossed over to the alternative treatment regimen. After 1 week of the alternate regimen, the subjects underwent a second methacholine challenge. Mean baseline values of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) and geometric mean value of provocative concentration of methacholine causing a 20% fall in FEV1 (PC20-FEV1) were equal between the first and the second methacholine test. The geometric mean value of PC20-FEV1 after the administration of ONO-1078 was 0.48 (geometric SEM, 1.48) mg ml-1, which was significantly (P < 0.01) greater than the value after the placebo administration (0.30 geometric SEM, 1.41 mg ml-1), but the baseline values of FVC and FEV1 were not altered by ONO-1078. We conclude that sulphidopeptide leukotrienes are significantly involved in the development of bronchial hyperresponsiveness in asthma but the degree of the involvement may be small.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / drug therapy*
  • Bronchial Hyperreactivity / physiopathology
  • Bronchial Provocation Tests
  • Chromones / therapeutic use*
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Lung / physiopathology
  • Male
  • Methacholine Chloride
  • Middle Aged
  • SRS-A / antagonists & inhibitors*
  • Vital Capacity / drug effects


  • Chromones
  • SRS-A
  • Methacholine Chloride
  • pranlukast