Abstract
Cysteinyl-leukotrienes are important mediators in the pathogenesis of asthma. Zafirlukast is a selective and competitive leukotriene receptor antagonist that has been developed for the treatment of asthma. It inhibits exercise-induced asthma, both the early- and late-phase response after allergen challenge in asthmatic subjects, and aspirin-induced asthma in aspirin-sensitive asthmatic patients. Published data indicate that zafirlukast 20 mg twice daily causes an improvement in lung function (FEV(1) and peak expiratory flow measurements) and symptom control, together with a reduction in the use of short-acting beta-agonist inhaled therapy in patients with mild to moderate asthma. Studies presented in abstract form have shown that zafirlukast 20 mg twice daily had similar efficacy as sodium cromoglycate aerosol or dry powder inhalation; in one of the studies, no advantage of the active drugs was reported over placebo. Compared to inhaled beclomethasone dipropionate therapy (200-250 microg b.i.d.), improvements in morning peak flow, FEV(1) and daytime symptom score were significantly less with zafirlukast 20 mg twice daily than with inhaled steroids. A steroid-sparing effect of zafirlukast (20 mg b.i.d.) was not observed in studies of 12-20 weeks duration in patients on inhaled steroid therapy. A significant improvement in lung function and symptom control was observed on addition of zafirlukast 80 mg twice daily in symptomatic patients maintained on high-dose inhaled steroid therapy. Meta-analysis of 5 large studies indicate that there is a significant reduction in the number of asthma exacerbations compared to placebo. Zafirlukast at 20 mg twice daily dosage appears to be well-tolerated comparable to placebo. High doses of 80 mg twice daily have been associated with reports of elevated liver enzymes. Zafirlukast is a useful addition to existing antiasthma therapies. It may be used in combination with inhaled or oral corticosteroid therapy. Further investigation of its efficacy and antiinflammatory effects will clarify its use as a first-line antiinflammatory agent in mild asthma. Zafirlukast is administered orally and may therefore be useful in patients poorly compliant with inhaled steroid therapy and with a poor inhaler technique.
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