Single-Dose Montelukast or Salmeterol as Protection Against Exercise-Induced Bronchoconstriction.

Author(s): Philip G, Pearlman DS, Villaran C, Legrand C, Loeys T, Langdon RB, Reiss TF

Affiliation(s): From the Merck Research Laboratories, Rahway, NJ, USA (Drs. Philip, Legrand, Loeys, Langdon, and Reiss; the Colorado Allergy and Asthma Centers, PC, Denver, CO (Dr. Pearlman); and the Clinica Ricardo Palma, Lima, Peru (Dr. Villaran).

Publication date & source: 2007-07-23, Chest., [Epub ahead of print]

Publication type:

Background and objective It has been previously established that montelukast provides protection against exercise-induced bronchoconstriction (EIB) after a single dose. The present objective was to assess the onset and duration of this protective action in a trial that included both positive and negative controls. Methods A randomized, active- and placebo-controlled, double-blind, double-dummy, 3-way crossover study was conducted in 47 patients (ages 15--44 years) in whom exercise induced a 20-40% fall in forced expiratory volume in 1 s (DeltaFEV(1)). In randomized sequence, patients received oral montelukast (10 mg), placebo, or inhaled salmeterol (50 mug) as a positive control. Dosing was followed by exercise challenges at 2, 8.5, and 24 h. The primary endpoint was maximum DeltaFEV(1) at 2 h postdose. Secondary endpoints included maximum DeltaFEV(1) at the 2 later timepoints, and other measures (including recovery time and need for beta-agonist rescue) at all timepoints. Results Maximum DeltaFEV(1) magnitudes at 2, 8.5, and 24 h were significantly smaller after montelukast than after placebo (LS-means +/- SE 13.2%+/-1.2%, 11.7%+/-1.2%, and 10.0%+/-1.1% versus 21.8%+/-1.2%, 16.8%+/-1.3%, and 14.0%+/-1.1%, respectively; p </= 0.001, < 0.01, and < 0.05). All secondary endpoint results supported the primary endpoint. Montelukast and salmeterol had similar efficacy at 2 and 8.5 h, but only montelukast was effective at 24 h. Conclusion Montelukast provided significant protection against EIB having an onset within 2 h following a single oral dose and lasting for at least 24 h.[Trial Registration: http://clinicaltrials.gov/show/NCT00245570].