Single-dose montelukast or salmeterol as protection against exercise-induced bronchoconstriction.
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 FEV(1) following exercise (DeltaFEV(1)). In randomized sequence, patients received oral montelukast (10 mg), placebo, or inhaled salmeterol (50 microg) as a positive control. Dosing was followed by exercise challenges at 2, 8.5, and 24 h. The primary end point was maximum DeltaFEV(1) at 2 h postdose. Secondary end points included maximum DeltaFEV(1) at the two later time points, and other measures (including recovery time and need for beta-agonist rescue) at all time points.


RESULTS
The maximum DeltaFEV(1) 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 <or= 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.


CONCLUSIONS
Montelukast provided significant protection against EIB having an onset within 2 h following a single oral dose and lasting for at least 24 h.
Philip
George
G
Merck Research Laboratories, Respiratory & Allergy Department, Mail code RY34B-348, 126 East Lincoln Ave, Rahway, NJ 07065, USA. george_philip@merck.com
Pearlman
David S
DS
Villarán
César
C
Legrand
Catherine
C
Loeys
Tom
T
Langdon
Ronald B
RB
Reiss
Theodore F
TF
D000085:Acetates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001982:Bronchial Diseases / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003251:Constriction, Pathologic / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015444:Exercise; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D011804:Quinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000068299:Salmeterol Xinafoate; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; D000068299:Salmeterol Xinafoate; C093875:montelukast; D000420:Albuterol