The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced bronchoconstriction in children.

OBJECTIVE: To determine the effects of zafirlukast on exercise-induced bronchoconstriction in children. STUDY DESIGN: Exercise challenges were done 4 hours after single oral doses of zafirlukast or placebo were administered in asthmatic children (6 to 14 years) treated with beta 2-agonists alone. Subjects randomized to treatment had a >/=20% decrease in forced expiratory volume in 1 second (FEV1 ) after a screening challenge. In a randomized, double-blind, 3-way, crossover design, group 1 (n = 20) received placebo and 5 and 20 mg zafirlukast, and group 2 (n = 19) received placebo and 10 and 40 mg zafirlukast. Maximal percentage fall in FEV1, area under the curve, and time to recovery of FEV1 to within 5% of baseline after the challenge were compared with analysis of variance. RESULTS: Mean values for maximal fall in FEV1 ranged from -8.7% +/- 1.7% to -11.1% +/- 1.9% after zafirlukast compared with -17.1% +/- 1.8% and -16.3% +/- 1.9% after placebo. Differences from placebo for fall in FEV1 and area under the curve were significant (P

Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction.

BACKGROUND: Previous trials demonstrated the effectiveness of the leukotriene receptor antagonist zafirlukast in patients with mild-to-moderate asthma. OBJECTIVES: We sought to assess the efficacy and safety of zafirlukast and its effect on patients' quality of life (QOL) during a 13-week, double-blind, placebo-controlled, multicenter trial in adults and adolescents with moderate reversible airflow obstruction. METHODS: Patients (age range, 12 to 68 years) with total daytime asthma symptoms scores of 10 or greater over 7 consecutive days (maximum, 21/wk), FEV1 45% or greater but less than or equal to 80% of predicted value (>/=6 hours after beta2 -agonist), and reversible airway disease were randomized to 20 mg zafirlukast twice daily (nZ = 231) or placebo twice daily (nP = 223). Efficacy was assessed from changes in daytime and nocturnal symptoms, beta2 -agonist use, nasal congestion score, and pulmonary function. QOL was evaluated with a disease-specific Asthma Quality of Life Questionnaire. Safety was determined from adverse event information and clinical laboratory test results. RESULTS: Zafirlukast was significantly (P <.001) more effective than placebo, with reductions from baseline in the daytime asthma symptoms score (-23%), nighttime awakenings with asthma (-19%), and beta2 -agonist use (-24%) and improvements from baseline in morning (+25 L/min) and evening (+18 L/min) peak expiratory flow rates. Compared with placebo, zafirlukast significantly (P /=0.5-unit change from baseline; P

A single dose of zafirlukast reduces LTD4-induced bronchoconstriction in patients on maintenance inhaled corticosteroid therapy.

BACKGROUND: Previous studies demonstrated that leukotriene receptor antagonists (LTRAs) are effective in reducing asthma symptoms and the airway response to inhaled leukotriene D4 (LTD4) in asthmatic patients receiving inhaled beta2-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 LTD4 in mild-to-moderate asthmatic patients receiving inhaled beta2-agonists and inhaled corticosteroids (ICS). METHODS: In this double-blind, crossover trial, six patients on maintenance ICS (median dose 800 microg/day; range 336 to 1600 microg/day), who had a 20% decrease in FEV1 following inhalation of a maximal concentration of 50 microg/mL LTD4, received either zafirlukast or placebo on each of two study days. Two hours after dosing, patients underwent bronchoprovocation challenges with increasing concentrations of LTD4 (0.1 to 1000 microg/mL) at 10-minute intervals until either the patient's FEV1 decreased by 20% or the maximum concentration of LTD4 was given. Spirometric tests were done just before (baseline) and throughout the challenge phase until the patient's FEV1 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 logPC20FEV1 and a 1.88-unit increase in logPD20FEV1, representing a 66-fold higher concentration and a 76-fold higher dose of LTD4, respectively, to produce a 20% decrease in FEV1 (P < .001). Mean time to recovery after challenge was 36.7 versus 51.7 minutes when patients received zafirlukast and placebo, respectively. No correlation between clinical effects and plasma drug levels was observed. CONCLUSIONS: This trial demonstrated that asthmatic patients on maintenance ICS can respond to exogenously administered LTD4 and that zafirlukast reduced the airway response to LTD4 in these patients.

Zafirlukast for symptomatic mild-to-moderate asthma: a 13-week multicenter study. The Zafirlukast Trialists Group.

The efficacy of the oral leukotriene-receptor antagonist zafirlukast was assessed as maintenance therapy for patients with mild-to-moderate asthma. A total of 762 patients aged 12 to 76 years were enrolled in a 13-week, multicenter, double-masked, placebo-controlled, parallel-group trial and randomly assigned to receive either zafirlukast (20 mg twice daily) or placebo. Patients were maintained on as-needed beta-agonist therapy throughout the study and had to have a cumulative daytime asthma symptoms score > or = 8 (on a daily scale of 0 to 3) over 7 consecutive days before randomization. Efficacy was assessed by changes in symptoms, beta-agonist use, and pulmonary function. Safety was assessed by adverse experiences, laboratory test results, physical examination, and electrocardiography. Zafirlukast significantly decreased daytime asthma symptoms scores (-26.5%), nighttime awakenings (-19.8%), mornings with asthma (-29.0%), and beta-agonist use (-22.3%) and significantly increased morning peak expiratory flow rate (6.9%) and forced expiratory volume in 1 second (6.3%) compared with placebo. Changes in symptoms, beta-agonist use, and pulmonary function occurred within 2 days of zafirlukast treatment and continued throughout the trial. Zafirlukast was well tolerated. Pharyngitis and headache were the most common adverse events, occurring with similar frequency in both the zafirlukast and placebo groups. No clinically significant changes were observed in laboratory test results, findings on physical examination, or electrocardiographic findings. We conclude that zafirlukast produces early and sustained effects in the treatment of mild-to-moderate asthma.