Inhibition of analgesic-induced asthma by leukotriene receptor antagonist ONO-1078

Am J Respir Crit Care Med. 1994 Jul;150(1):254-7. doi: 10.1164/ajrccm.150.1.8025759.


We evaluated the effect of ONO-1078, a selective leukotriene-C4, -D4, and -E4-receptor antagonist, on bronchoconstriction intensity during inhalation challenge with dipyrone (a pyrazolone derivative) in six aspirin-sensitive asthmatics. A double-blind, randomized, crossover design was used. After ingestion of 225 mg ONO-1078 or matching placebo, subjects underwent bronchial provocation with dipyrone on two occasions, separated by 4 wk. Aerosol inhalation of dipyrone was performed increasing the concentration stepwise from 0.08 to 10% (wt/vol). FEV1 was measured every 10 min up to 30 min after inhalation of each concentration. Threshold concentrations causing a fall in FEV1 > or = 20% of baseline value were 0.4% in four subjects and 2% in the other two on the placebo day. After pretreatment with ONO-1078, threshold concentration was 10% in two subjects, and no fall in FEV1 was observed in the other four, even after inhalation of 10% dipyrone. Values of PD20 were 21.9 +/- 8.2 units (mean +/- SEM) after placebo and 311.6 +/- 40.3 units after ONO-1078, respectively, and a statistically significant difference occurred (p < 0.001). Provocation of bronchoconstriction was completely inhibited in subjects whose plasma ONO-1078 levels were more than 0.5 microgram/ml. These results support the hypothesis that sulfidopeptide leukotriene-induced bronchoconstriction is one important component in the pathophysiology of aspirin-induced asthma.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aspirin / adverse effects*
  • Asthma / chemically induced
  • Asthma / physiopathology*
  • Asthma / prevention & control
  • Bronchial Provocation Tests
  • Bronchoconstriction / drug effects
  • Chromones / therapeutic use*
  • Dipyrone
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • SRS-A / antagonists & inhibitors*


  • Chromones
  • SRS-A
  • Dipyrone
  • Aspirin
  • pranlukast