The present study was designed to evaluate the bronchodilating role of
zafirlukast, a
CysLT(1)receptor antagonist, at the standard dosage currently recommended in the marketing of this agent in smokers with
COPD. The study was performed using a double-blind, cross-over, randomized design and was conducted on 2 non-consecutive days. Sixteen outpatients suffering from stable
COPD received 40 mg oral
zafirlukast, or placebo. Lung function was controlled before
drug administration and 30, 60, 120, 180, 240 min thereafter. At the end of the 4-h period, each patient received 400 microg inhaled
salbutamol and spirometric testing was performed 30 min later.
Zafirlukast, but not placebo, produced a significant (P<0.05) bronchodilation between 30 min and 4 h following administration, with a maximum mean increase in FEV(1)of 0.134 l (11.2%) above baseline after 2 h. Nine of 16 patients showed an increase in FEV(1)of at least 15% above baseline after
zafirlukast. The maximum mean increase in FEV(1)after
zafirlukast in these subjects, who were considered responders, observed after 2 h, was 0.221 (19.4%). The mean difference of post-
salbutamol FEV(1)values after
zafirlukast and placebo (-0.036 l) was not significant (P<0.05). In responders, the mean of differences in pre- and post-
salbutamol FEV(1)values after
zafirlukast was 0.077 l, whereas the mean of differences between post-
salbutamol values after
zafirlukast and those after placebo was -0.064 l. The mean AUC(0-4 h)for all patients was 0.121 l for placebo and 0.385 l for
zafirlukast. The difference between the placebo and
zafirlukast AUC(0-4 h)was significant (P<0.05). The individual FEV(1)AUC(0-4 h)after
zafirlukast were higher than those after placebo in 12 out of 16 patients. These findings suggest that cysteinyl
leukotrienes might be one of the causes of persistent bronchoconstriction in
COPD, at least in several smokers, but do not confirm the hypothesis that the effects of
zafirlukast and
salbutamol are independent and additive.