ACUTE BRONCHODILATION WITH AN INTRAVENOUSLY ADMINISTERED LEUKOTRIENE-D(4) ANTAGONIST, MK-679

Descriptive studies suggest an association between the release of the cysteinyl leukotrienes and clinical asthma. To help clarify this assoc iation, we tested the hypothesis that an intravenous infusion of a pot ent and specific investigational LTD4 receptor antagonist, MK-679, wou ld cause rapid bronchodilation. In a three-period, randomized, double- blind, crossover study, single doses of MK-679,125 and 500 mg, and pla cebo were given intravenously by bolus infusion to nine patients with moderate, stable asthma (FEV1 40 to 80% predicted) on individual study days separated by a week. Spirometry was performed predose and at int ervals for as long as 8 h postdosing; blood samples for MK-679 concent rations were drawn over this time. Fifteen minutes after the end of in fusion, the FEV1 percent change from baseline increased a mean of 15.8 +/- 15.7 and 7.8 +/- 11.6% with the 500- and 125-mg doses, respective ly, compared with a mean decrease of 2.6 +/- 6.2% with placebo (p = 0. 01, overall; p = 0.003, 500 mg versus placebo). The mean end-of-infusi on MK-679 plasma concentrations were 86.2 +/- 13.9 and 19.9 +/- 2.7 mu g/ml for the 500- and 125-mg doses, respectively. MK-679 was well-tole rated, with no significant adverse experiences observed. We conclude t hat a single, intravenously administered, bolus infusion of MK-679 cau ses bronchodilation in patients with moderate, stable asthma.