Management of asthma with zafirlukast. Clinical experience and tolerability profile

This article reviews the literature on the use of zafirlukast in the treatment of asthma, with particular focus on its ability to attenuate the asthma-causing effects of leukotrienes. Leukotrienes produced by the 5-lipoxygenase enzyme pathway have various biological activities. These include the specific inflammatory effects associated with asthma, such as increased vascular permeability, enhanced mucus production and decreased mucociliary transport. Leukotriene receptors in the airways also mediate a potent bronchoconstriction and this is particularly important in asthma. Zafirlukast was developed with the goal of attenuating the inflammatory effects of leukotrienes in asthma. Zafirlukast attenuates the responses to inhaled leukotrienes and allergen challenges, and produces beneficial effects in cold air- and exercise-induced asthma. Zafirlukast has been compared with placebo and sodium cromoglycate in clinical trials involving asthma patients. Zafirlukast brings about a significant bronchodilation within 1 hour of administration that is additive to the effects of beta 2 agonists. These studies showed that zafirlukast improves pulmonary function and reduces the symptoms of asthma. Zafirlukast is well tolerated with an incidence of adverse events similar to that seen with the use of placebo. As an oral twice-daily formulation, zafirlukast may improve patient adherence to therapy. As an anti-inflammatory agent, zafirlukast may in the future find a role in the treatment of a variety of diverse inflammatory conditions.