B. Dahlen et al., EFFECT OF THE LEUKOTRIENE RECEPTOR ANTAGONIST MK-0679 ON BASE-LINE PULMONARY-FUNCTION IN ASPIRIN-SENSITIVE ASTHMATIC SUBJECTS, Thorax, 48(12), 1993, pp. 1205-1210
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.