Additive bronchoprotective and bronchodilator effects with single doses ofsalmeterol and montelukast in asthmatic patients receiving inhaled corticosteroids

Objective: We wished to evaluate whether the combination of a leukotriene r eceptor antagonist and long-acting beta(2)-agonist might confer additive be neficial effects in terms of bronchoprotection and bronchodilatation, in mi ld to moderate asthmatic patients who were suboptimally controlled on inhal ed corticosteroids alone. Methods: Twelve asthmatic patients were enrolled into a single-blind, place bo-controlled, crossover study, receiving additive therapy as either of the following: (1) montelukast alone, 10 mg (ML10); (2) inhaled salmeterol alo ne, 50 mu g (SM50); (3) ML10 and SM50; (4) ML10, and inhaled salmeterol, 10 0 mu g (SM100); or (5) placebo inhaler and tablet. Trough measurements were made of adenosine monophosphate (AMP) bronchial challenge (the provocative concentration of a drug [AMP] causing a fall of greater than or equal to 2 0% in FEV1 [PC20]) as the primary end point, and spirometry, following sing le doses of either placebo or active treatments (12 h after salmeterol, and 24 h after monteleukast, respectively). Results: Compared to placebo, all active treatments led to significant impr ovements (p < 0.05) in geometric mean AMP-PC20: placebo, 42 mg/mL; ML10, 10 6 mg/mL; SM50, 115 mg/ML; ML10 and SM50, 183 mg/mL; and ML10 and SM100, 247 mg/mL. The effects of montelukast and salmeterol were numerically additive , with ML10 and SM100 being significantly different (p < 0.05) from ML10 al one. For mean FEV1 and forced expiratory flow rate between 25% and 75% of v ital capacity, there were significant differences (p < 0.05) between both c ombination therapies vs ML10 alone. Conclusions: Our results suggest additive benefits of a single dose of a lo ng-acting beta(2)-agonist and leukotriene antagonist, in terms of bronchopr otection and bronchodilation. Further studies in more severe asthmatics are required to evaluate long-term clinical effects.