EFFECTS OF MONTELUKAST (MK-0476), A NEW POTENT CYSTEINYL LEUKOTRIENE (LDT(4)) RECEPTOR ANTAGONIST, IN PATIENTS WITH CHRONIC ASTHMA

Background: Cysteinyl leukotrienes mediate signs and symptoms of asthm a. In a double-blind, placebo-controlled, crossover study, a new poten t and specific cysteinyl leukotriene (LTD(4)) receptor antagonist, mon telukast (MK-0476), was evaluated for tolerability and clinical effica cy in patients with chronic asthma (receiving and not receiving inhale d corticosteroids). Methods: Twenty-nine nonsmoking patients with asth ma (15 treated concomitantly with inhaled corticosteroids) with FEV(1) percent predicted values between 50% to 80% received MK-0476, 200 mg, or placebo three times daily for 10 1/3 days (31 doses) in a random, crossover manner, after a 2-week, open, baseline period. Comparisons i n FEV(1) (mean percent change from baseline after the first and last d ose), mean daily daytime asthma and nocturnal awakening scores, and me an daily beta-agonist use were made between treatment periods. Results : Montelukast, compared with placebo, caused improvements in FEV(1) (m ean percentage point difference of the percentage change from baseline ) 3 and 4 hours after dosing on day 1 (hour 3, 9.0%; 95% confidence in terval [CI] 0.53, 18.72; hour four, 10.9%; 95% CI -0.25, 20.20) and da y 11 (hour 3, 14.0%; 95% CI 0.76, 31.43; hour 4, 13.4%; 95% CI 1.24, 2 8.83). Reductions were observed in mean daily beta-agonist use (1.0 pu ff/day [95% CI -1.61, -0.26]), mean daytime symptom scores, and noctur nal awakenings over the 10 1/3 day treatment period. There were no imp ortant differences between the groups receiving and those not receivin g inhaled corticosteroids. Montelukast was well tolerated with no seri ous clinical adverse events reported. Conclusions: In this study Monte lukast, 200 mg, administered three times daily for 10 1/3 days, compar ed with placebo, was generally well tolerated and resulted in signific ant improvement in chronic asthma, irrespective of the presence of inh aled corticosteroids.