Onset and duration of protection against exercise-induced bronchoconstriction by a single oral dose of montelukast.
BACKGROUND
Leukotriene modifiers have been shown to protect against exercise-induced bronchoconstriction (EIB) with repeated, chronic dosing.


OBJECTIVE
To study the onset and duration of protection against EIB after a single dose of montelukast, a leukotriene receptor antagonist.


METHODS
In this randomized, crossover, double-blind study, 51 adult asthma patients with EIB (> or = 20% postexercise decrease in forced expiratory volume in 1 second [FEV1]) received a single oral dose of montelukast (10 mg), or placebo followed by exercise challenge 2, 12, and 24 hours after dosing. The primary end point was maximum percentage decrease in FEV1 from preexercise baseline during 60 minutes after the 2-hour challenge.


RESULTS
At 2, 12, and 24 hours after dosing, the maximum decrease in FEV1 was 10.8% +/- 7.9%, 8.4% +/- 7.5%, and 8.3% +/- 7.3% for montelukast and 22.3% +/- 13.1%, 16.1% +/- 10.2%, and 16.9% +/- 11.7% for placebo, respectively (P < or = .001 at each time point). Postexercise recovery was quicker with montelukast than with placebo (P < or = .001); mean (95% confidence interval) differences were -26.8 minutes (-35.1 to -18.4 minutes), -16.0 minutes (-22.9 to -9.2 minutes), and -17.4 minutes (-24.9 to -9.9 minutes) at the 3 time points, respectively. At all time points, area under the curve for percentage decrease in FEV1 during 60 minutes after exercise was smaller after montelukast (P < or = .001); montelukast protected more patients against EIB (P < or = .001). Fewer patients required postexercise beta-agonist rescue at 2 hours after dosing with montelukast (P = .03).


CONCLUSIONS
Montelukast provided significant protection against EIB as soon as 2 hours after a single oral dose, with persistent benefit up to 24 hours.
Pearlman
David S
DS
Colorado Allergy and Asthma Centers, PC, Denver, Colorado 80230, USA. ds.pearlman@coloradoallergy.com
van Adelsberg
Janet
J
Philip
George
G
Tilles
Stephen A
SA
Busse
William
W
Hendeles
Leslie
L
Loeys
Thomas
T
Dass
S Balachandra
SB
Reiss
Theodore F
TF
D000085:Acetates / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000328:Adult; D019540:Area Under Curve; D001250:Asthma, Exercise-Induced / Q000188:drug therapy / Q000517:prevention & control*; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D013440:Sulfides; D013997:Time Factors
D000085:Acetates; D000318:Adrenergic beta-Agonists; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast