Inhibition of analgesic-induced asthma by leukotriene receptor antagonist ONO-1078.
Am J Respir Crit Care Med
; 150(1): 254-7, 1994 Jul.
Article
em En
| MEDLINE
| ID: mdl-8025759
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Asma
/
SRS-A
/
Aspirina
/
Cromonas
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
1994
Tipo de documento:
Article