Influence of higher than conventional doses of oxitropium bromide on formoterol-induced bronchodilation in COPD

Abstract

We examined the influence of higher than conventional doses of oxitropium bromide on formoterol-induced bronchodilation in patients with partially reversible stable COPD. Twenty outpatients inhaled one or two puffs of formoterol (12 μg puff −1), or placebo. Two hours after inhalation, a dose-response curve to inhaled oxitropium bromide (100 μg puff −1) or placebo was constructed using one puff, one puff, two puffs and two puffs, for a total cumulative dose of 600 μg oxitropium bromide. Doses were given at 20-min intervals and measurements made 15 min after each dose. On six separate days, all patients received one of the following: (1) formoterol 12 μg + oxitropium bromide 600 μg, (2) formoterol 12 μg + placebo, (3) formoterol 24 μg + oxitropium bromide 600 μg, (4) formoterol 24 μg + placebo, (5) placebo + oxitropium bromide 600 μg, or (6) placebo + placebo. Both formoterol 12 μg and 24 μg induced a good bronchodilation (formoterol 12 μg, 0·19–0·20 1; formoterol 24 μg 0·22–0·24 1). The dose-response curve of oxitropium, but not placebo, showed an evident increase in FEV 1, with a further significant increase of respectively 0·087 1 and 0·082 1 after the formoterol 12 μg and formoterol 24 μg pre-treatment. This study shows that improved pulmonary function in patients with stable COPD may be achieved by adding oxitropium 400–600 μg to formoterol. There is not much difference in bronchodilation between combining oxitropium with formoterol 12 μg or 24 μg. In any case, formoterol 24 μg alone seems sufficient to achieve the same bronchodilation induced by oxitropium 600 μg alone in most patients.