Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction

Objective—To evaluate whether the leukotriene (LT) D4 receptor antagonist L-708,738 is therapeutically beneficial in treating horses with recurrent airway obstruction (heaves). Animals—12 adult horses with heaves and healthy lung lobes from 20 slaughtered horses. Procedure—Lung lobes were used for smooth muscle tension and radioligand binding studies. Horses with heaves were given a placebo for 14 days and administered L-708,738 (n = 6; 2.5 mg/kg PO, q 12 h) or dexamethasone (6; 0.04 mg/kg, IV, q 24 h) from days 14 to 28. Pulmonary function was measured weekly for 36 days, and bronchoalveolar cells were collected on days 0, 14, and 29 for cytologic examination. Results—Nanomolar concentrations of L-708,738 were effective at antagonizing LTD4-induced bronchoconstriction and LTD4-receptor binding in lung lobes. Mean peak and trough L-708,738 plasma concentrations during the treatment period were 1.54 and 0.28 μM, respectively. On days 21 and 29, lung mechanics were significantly improved in the dexamethason...