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.
Third Department of Internal Medicine, Kanazawa University, School of Medicine, Japan.
M
M
Fujimura
S
S
Sakamoto
Y
Y
Kamio
T
T
Matsuda
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