Montelukast

Abstract

The CYS-LTs are lipid products of arachidonic acid that are generated primarily by mast cells, eosinophils, basophils, and monocytes. Their potent activity in contracting human bronchial smooth muscle has been recognized for 60 years as 'slow-reacting substance', and their pro-inflammatory actions include mucus hypersecretion, vascular edema, neuropeptide release, bronchial hyperresponsiveness, and infiltration of the airways by leukocytes, particularly eosinophils. Levels of Cys-LTs are increased in the BAL fluid, induced sputum and urine of asthmatic subjects following allergic and other inhaled challenges and during spontaneous acute exacerbations. Montelukast sodium (Singulair®) is a potent and specific oral antagonist of the Cys-LT-type 1 receptor (Cys-LT1), which mediates the bronchoconstrictor and other pro-inflammatory activities of Cys-LTs. The drug is available as 10 mg tablets for adults (14 years), 5 mg for children (6-14 years), and 4 mg for infants (2-5 years), taken once-daily at bedtime. In bronchoprovocation studies, montelukast significantly reduces bronchoconstriction induced by allergen, exercise/cold air and NSAIDs in susceptible individuals. In clinical trials in adults and children with persistent asthma, oral montelukast produces improvements in baseline lung function, frequency of acute exacerbations, daily symptom scores, night-time awakenings, days lost from work/school, use of rescue medication (β2-agonists, oral prednisolone), and quality-of-life. The efficacy of montelukast is comparable to that of modest doses of an inhaled glucocorticosteroid, but additive beneficial effects are observed even in patients receiving high doses of ICS and β2-bronchodilators, suggesting that montelukast blocks mechanisms not targeted by the other drugs. Montelukast has a good safety profile, with mild headache, URTI and gastrointestinal upset being the adverse events most commonly reported in clinical trials. Evidence for a corticosteroid-sparing effect of montelukast is emerging, but precipitate withdrawal of OCS on introducing montelukast may be associated in rare cases with emergence of occult Churg-Strauss syndrome. The oral formulation and once-daily dosing schedule of montelukast contribute to good patient adherence compared to inhaled drugs, and it has entered national and international treatment guidelines for asthma therapy. Clinical trials of montelukast in allergic rhinitis and other inflammatory conditions are increasing our knowledge of the role of Cys-LTs in these diseases.