Zafirlukast: A Cysteinyl Leukotriene Receptor Antagonist for Asthma

Abstract

Zafirlukast is a selective cysteinyl leukotriene receptor antagonist for the treatment of asthma. It acts by binding competitively to cysLT₁ receptor against endogenous leukotrienes which cause bronchospasm. Administration should be on an empty stomach because food lowers its oral bioavailability. Elimination is mostly by the liver through CYP2C9 with a half-life of 10 h. The metabolites are excreted through the bile into feces. Zafirlukast relieves leukotrine-induced bronchoconstriction in animals and those induced by allergens, exercise and cold air in humans. Clinical trials show that zafirlukast improves symptoms, peak expiratory flow rate and FEV₁ in chronic asthma. These effects are similar to cromolyn sodium but less than those achieved by fluticasone and salmeterol. Bronchoalveolar lavage findings suggest that it has some anti-inflammatory effects. The most common adverse effects are sorethroat, headache and worsening of asthma symptoms. Normal doses do not increase the levels of hepatic transaminases whereas induction of Churg-Strauss syndrome is controversial. Drug interactions occur with co-administration of aspirin, erythromycin, theophylline and warfarin. Zafirlukast is indicated in older children and adults with chronic asthma with inadequate response to inhaled corticosteroids, prevention of exercise-induced asthma and treatment of aspirin induced asthma, but should not be used in acute asthmatic attack.