Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction. A randomized, double-blind trial. Exercise Study Group.
BACKGROUND
Montelukast, an oral, once-daily leukotriene receptor antagonist, provides protection against exercise-induced bronchoconstriction.


OBJECTIVE
To evaluate the effect of 8 weeks of therapy with salmeterol aerosol or montelukast on exercise-induced bronchoconstriction in adults with asthma.


METHODS
8-week multicenter, randomized, double-blind study.


METHODS
17 asthma treatment centers in the United States.


METHODS
191 adults with asthma who had documented exercise-induced bronchoconstriction.


METHODS
Qualified patients were randomly assigned to double-blind treatment with montelukast (10 mg once in the evening) or salmeterol (50 microg [2 puffs] twice daily).


METHODS
Changes in pre-exercise and postexercise challenge values; percentage inhibition in the maximal percentage decrease in FEV1; the area above the FEV1-time curve; and time to recovery of FEV1 at days 1 to 3, week 4, and week 8 of treatment.


RESULTS
By day 3, similar and statistically significant reductions in maximal percentage decrease in FEV1 were seen with both therapies. Sustained improvement occurred in the montelukast group at weeks 4 and 8; at these time points, the bronchoprotective effect of salmeterol decreased significantly. At week 8, the percentage inhibition in the maximal percentage decrease in FEV1 was 57.2% in the montelukast group and 33.0% in the salmeterol group (P = 0.002). By week 8, 67% of patients receiving montelukast and 46% of patients receiving salmeterol had a maximal percentage decrease in FEV1 of less than 20%.


CONCLUSIONS
The bronchoprotective effect of montelukast was maintained throughout 8 weeks of study. In contrast, significant loss of bronchoprotection at weeks 4 and 8 was seen with salmeterol. Long-term administration of montelukast provided consistent inhibition of exercise-induced bronchoconstriction at the end of the 8-week dosing interval without tolerance.
Edelman
J M
JM
Merck & Co., Inc., West Point, Pennsylvania 19486, USA. edelmanj@merck.com
Turpin
J A
JA
Bronsky
E A
EA
Grossman
J
J
Kemp
J P
JP
Ghannam
A F
AF
DeLucca
P T
PT
Gormley
G J
GJ
Pearlman
D S
DS
D000085:Acetates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001250:Asthma, Exercise-Induced / Q000503:physiopathology / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000068299:Salmeterol Xinafoate; D013440:Sulfides
D000085:Acetates; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D000068299:Salmeterol Xinafoate; C093875:montelukast; D000420:Albuterol