A Single Dose of Zafirlukast Reduces LTD4-Induced Bronchoconstriction in Patients on Maintenance Inhaled Corticosteroid Therapy

Background Previous studies demonstrated that leukotriene receptor antagoinist (LTRAs) are effective in reducing asthma symptoms and the airway response to inhaled leukotriene D 4 (LTD 4 ) in asthmatic patients receiving inhaled beta 2 -agonists alone. Objective To investigate the efficacy of a single 20-mg dose of the oral LTRA zafirlukast in reducing the airway response to inhaled LTD 4 in mild-to-moderate asthmatic patients receiving inhaled beta 2 -agonists and inhaled coritcosteroids (ICS). Methods In this double-blind, crossover trial, six patients on maintenance ICS (median dose 800 micrograms/d; range 336 to 1600 micrograms/d), who had a 20% decrease in FEV 1 following inhalation of a maximal concentration of 50 micrograms/mL LTD 4 , received either zafirlukast or placebo on each of two study days. Two hours after dosing, patients underwent bronchoprovocatoin challenges with increasing concentrations of LTD 4 (0.1 to 1000 micrograms/mL) at 10-minute intervals until either the patient's FEV 1 increased by 20% or the maximum concentration of LTD 4 was given. Spirometric tests were done just before (baseline) and throughout the challenge phase until the patient's FEV 1 returned to within 5% of baseline. Blood samples were collected two hours after dosing to determine plasma concentrations of zafirlukast. Results Compared with placebo, zafirlukast produced a 1.82-unit increase in logPC 20 FEV 1 and a 1.88-unit increase in logPD 20 FEV 1 , representing a 66-fold higher concentration and a 76-fold higher dose of LTD 4 , respectively, to produce a 20% decrease in FEV 1 ( P Conclusions This trial demonstrated that asthmatic patients on maintenance ICS can respond to exogenously administered LTD 4 and that zafirlukast reduced the airway response to LTD 4 in these patients.