Inhibition of analgesic-induced asthma by leukotriene receptor antagonist ONO-1078.
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.
Second Department of Internal Medicine, Saitama Medical School, Japan.
H
H
Yamamoto
M
M
Nagata
K
K
Kuramitsu
K
K
Tabe
H
H
Kiuchi
Y
Y
Sakamoto
K
K
Yamamoto
Y
Y
Dohi
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D002867:Chromones / Q000627:therapeutic use*; D004177:Dipyrone; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D013189:SRS-A / Q000037:antagonists & inhibitors*
D002867:Chromones; D013189:SRS-A; D004177:Dipyrone; D001241:Aspirin; C047681:pranlukast