Zafirlukast (Accolate®): A review of its pharmacological and clinical profile

Abstract

Today, bronchial asthma is considered as a chronic inflammatory disease of the airway. It has been revealed that various chemical mediators are involved in the onset of bronchial asthma. Among them, particularly, the peptide leukotrienes, LTC 4, LTD 4 and LTE 4, have been known to play a pathophysiological important role in asthma. Zafirlukast binds to the CysLT 1 receptors competitively with these peptide leukotrienes and inhibited peptide leukotriene-induced constriction of isolated guinea pig trachea and lung parenchyma and isolated human bronchi. Zafirlukast also demonstrated dose-dependent inhibition of LTD 4-induced dyspnea in guinea pigs in vivo. Zafirlukast demonstrated preventive and alleviating effects on LTD 4- and ovalbumin-induced decrease in the lung function. Zafirlukast also displayed inhibitory effects on LTD 4-induced eosinophil infiltration into airway tissues and bronchial edema. In sheep naturally allergic to Ascaris suum antigen, zafirlukast exhibited inhibitory effects on Ascaris suum antigen-induced immediate and late type airway constriction and increase in airway hypersensitivity. In clinical pharmacology studies, zafirlukast inhibited LTD 4- or allergen-induced airway constriction and exercise-induced reduction of the pulmonary function. It also prevented onset of methacholine-induced airway hyperresponsiveness. Furthermore, good efficacy of zafirlukast was confirmed in clinical trials in adult bronchial asthma patients. As above, zafirlukast is effective for treatment of bronchial asthma, which is attributed to its peptide leukotriene antagonistic action.