Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D-4-receptor antagonist cinalukast

Objectives: The degree and duration of protection against exercise-induced bronchoconstriction afforded by three doses of a specific leukotriene D-4 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 made 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 Fev(1)-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 cinalukast was lost after 7 days of treatment but persisted with 50 mg and 200 mg doses. Conclusion: 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.