Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D4-receptor antagonist cinalukast.
OBJECTIVE
The degree and duration of protection against exercise-induced bronchoconstriction afforded by three doses of a specific leukotriene D4 receptor antagonist, cinalukast, were assessed after an initial dosing and after 1 week of therapy.


METHODS
A placebo-controlled crossover study was performed in eight male patients who had mild, stable asthma and exercise-induced bronchoconstriction. Treatment consisted of four 7-day periods of placebo and three dose levels of the drug (10, 50, and 200 mg administered orally). Exercise challenge was performed at 2 hours and 8 hours after treatment on the first and seventh treatment days. The response was measured as the area under the FEV1-time effect curve (AUEC).


RESULTS
On the first day of treatment, the mean (+/- SEM) AUEC at 2 hours was 24.2 +/- 3.3 L.min after placebo and was 5.5 +/- 2.2 L.min, 6.3 +/- 2.7 L.min, 3.3 +/- 3.8 L.min after 10 mg, 50 mg, and 200 mg, respectively (p < 0.05 for all values compared with placebo). The AUEC at 8 hours on the first day was 25.1 +/- 4.4 L.min after placebo and was 6.8 +/- 4.1 L.min, 11.2 +/- 2.5 L.min, and 5.0 +/- 2.8 L.min after 10 mg, 50 mg, and 200 mg, respectively (p < 0.05 for all values compared with placebo). The protection afforded by 10 mg of cinaluicast was lost after 7 days of treatment but persisted with 50 mg and 200 mg doses.


CONCLUSIONS
Orally administered cinalukast provides at least 8 hours of protection against exercise-induced bronchoconstriction. This protection is lost with regular treatment for 1 week for the lowest dose studied.
Adelroth
E
E
Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
Inman
M D
MD
Summers
E
E
Pace
D
D
Modi
M
M
O'Byrne
P M
PM
D000284:Administration, Oral; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001250:Asthma, Exercise-Induced / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005080:Exercise Test; D006801:Humans; D020024:Leukotriene Antagonists; D008297:Male; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D012129:Respiratory Function Tests; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors
D018927:Anti-Asthmatic Agents; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D013844:Thiazoles; C071436:cinalukast; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor