EFFECT OF THE LEUKOTRIENE RECEPTOR ANTAGONIST MK-0679 ON BASE-LINE PULMONARY-FUNCTION IN ASPIRIN-SENSITIVE ASTHMATIC SUBJECTS

Background-The cysteinyl leukotrienes (LTC(4), LTD(4), and LTE(4)) hav e been to mediate airway obstruction evoked by several factors which t rigger asthmatic reactions-for example, allergen and exercise. Accordi ngly, drugs which block the action or formation of these leukotrienes are being evaluated as a new treatment of asthma. Elevated production of leukotrienes has been reported in asthmatic subjects who are intole rant to aspirin and related nonsteroidal anti-inflammatory drugs. In t his study the influence of the specific leukotriene receptor antagonis t MK-0679 was tested on basal airway function in asthmatic patients wi th documented aspirin intolerance. Methods-The eight subjects in the s tudy had a mean baseline FEV, of predicted (range 58-99%) and required treatment with inhaled glucocorticosteroids (400-1200 mu g budesonide /beclomethasone daily). On two separate days the subjects received eit her 825 mg MK-0679 or placebo, orally in a double blind, randomised, c rossover design. Results-The leukotriene antagonist MK-0679 caused bro nchodilation which lasted for at least nine hours. The average peak im provement in FEV, was 18% above the predrug baseline, but the bronchod ilator response varied between 34% and 5% and was found to correlate s trongly with the severity of asthma and aspirin sensitivity. Conclusio ns-The findings indicate that ongoing leukotriene production may be on e cause of persistent airway obstruction in aspirin sensitive asthmati c subjects and that they may benefit from treatment with a leukotriene receptor antagonist.