Comparison of the bronchodilating effect of salmeterol and zafirlukast in combination with that of their use as single treatments in asthma and chronic obstructive pulmonary disease

Background. It has been suggested that the effect of a beta (2)-agonist is additive with that of a cysteinyl leukotriene 1 receptor antagonist. Object ives: The present study was designed to answer the question of whether comb ined administration of inhaled salmeterol and oral zafirlukast at the stand ard doses would result in greater bronchodilation in patients with chronic airway obstruction than the use of either drug alone. Methods: The study wa s per-formed using a double-blind, double-dummy, crossover, randomised desi gn, and was conducted on 4 nonconsecutive days. Sixteen patients with moder ate to severe chronic obstructive pulmonary disease (COPD) and 10 non-smoke r asthmatic patients received 40 mg of oral zafirlukast, 50 mug of inhaled salmeterol, 50 mug of inhaled salmeterol plus 40 mg of oral zafirlukast of placebo. Lung function was assessed before drug administration and 30, 60, 120, 180 and 240 min thereafter. At the end of the 4-hour period, each pati ent received 400 mug of inhaled salbutamol and spirometric testing was perf ormed 30 min later. Results: In both asthmatic and COPD patients, the overa ll effect of salmeterol and zafirlukast on the forced expiratory volume in 1 s (FEV1) was considered extremely significant (p < 0.0001), with a maximu m bronchodilation above baseline after 180 min (20.7 and 11.0%, respectivel y) in asthmatics and after 2 h (21.7 and 11.2%, respectively) in COPD subje cts. Zafirlukast did not produce any further significant acute bronchodilat ion in addition to that achieved with salmeterol alone in either asthmatic or COPD patients. Nevertheless, 7 out of 16 COPD patients and 7 out of 10 a sthmatic patients had a further improvement after the combination of salmet erol and zafirlukast. The mean difference in pre- and post-salbutamol FEV, values in both asthmatic and COPD patients after zafirlukast was significan t (p < 0.05), but that after salmeterol and the combination of the two drug s was not significant (p > 0.05). The difference between placebo and zafirl ukast was not significant following inhaled salbutamol given 4 h after each treatment. Conclusions: Both salmeterol and zafirlukast induced a signific ant increase in FEV1, although salmeterol elicited a greater improvement in both asthmatic and COPD patients. Apparently, zafirlukast at the clinicall y recommended dose did not produce any further significant acute bronchodil ation in addition to that achieved with salmeterol alone, either in asthma or COPD. In any case, evaluation of the effect of the combination over a 12 -hour period is mandatory. Copyright (C) 2001 S. Karger AG, Basel.