Effect of a leukotriene antagonist, ONO-1078, on bronchial hyperresponsiveness in patients with asthma.
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.
Fujimura
M
M
Third Department of Internal Medicine, Kanazawa University, School of Medicine, Japan.
Sakamoto
S
S
Kamio
Y
Y
Matsuda
T
T
D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D002867:Chromones / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D013189:SRS-A / Q000037:antagonists & inhibitors*; D014797:Vital Capacity / Q000187:drug effects
D002867:Chromones; D013189:SRS-A; D016210:Methacholine Chloride; C047681:pranlukast