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

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

Correspondence to: George Philip, MD, Merck Research Laboratories, Respiratory & Allergy Department, Mail code RY34B-348, 126 East Lincoln Ave, Rahway, NJ 07065; e-mail: george_philip{at}merck.com

Abstract

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-controlled and placebo-controlled, double-blind, double-dummy, three-way crossover study was conducted in 47 patients (age range, 15 to 44 years) in whom there was a 20 to 40% fall in FEV₁ following exercise (FEV₁). In randomized sequence, patients received oral montelukast (10 mg), placebo, or inhaled salmeterol (50 µg) as a positive control. Dosing was followed by exercise challenges at 2, 8.5, and 24 h. The primary end point was maximum FEV₁ at 2 h postdose. Secondary end points included maximum FEV₁ at the two later time points, and other measures (including recovery time and need for ß-agonist rescue) at all time points.

Results: The maximum FEV₁ magnitudes at 2, 8.5, and 24 h were significantly smaller after montelukast administration than after placebo administration (least squares mean [± SE], 13.2 ± 1.2%, 11.7 ± 1.2%, and 10.0 ± 1.1% vs 21.8 ± 1.2%, 16.8 ± 1.3%, and 14.0 ± 1.1%, respectively; p 0.001, < 0.01, and < 0.05). All secondary end point results supported the primary end point. 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.

Key Words: ß-adrenergic receptor agonist • bronchial asthma • bronchospasm • exercise-induced bronchoconstriction • leukotriene receptor antagonist • long-acting ß-agonist