Oxitropium bromide: Dose-response and time-response study of a new anticholinergic bronchodilator drug

The efficacy and side effects of oxitropium bromide, a new anticholinergic bronchodilator drug, were tested in a double-blind placebo-control study. Twenty-four men, aged 58 to 72 years, with chronic partially reversible obstruction of the airways were used as subjects. Three doses of oxitropium were tested (100μg, 200μg, and 300μg) to determine the optimum dose by metered-dose inhaler. A comparison was also made between oxitropium, fenoterol (400μg), and a combination of oxitropium (200μg) and fenoterol (400μg). Fenoterol produced a greater degree of maximal bronchodilatation than each of the three doses of oxitropium, and its effect was more rapid in onset (30 vs 120 minutes to peak effect); however, the duration of action of oxitropium was greater than that of fenoterol (ie, the forced respiratory volume in one second [FEV₁] remained within 5 percent of peak FEV₁ for three hours, compared to one hour). Oxitropium in the 100μg dose was inferior to 200μg and 300μg in subjective efficacy scores, peak percent change in FEV₁, forced vital capacity, (FVC), mean forced expiratory flow over the middle half of the FVC, and duration of action; there was no difference between 200μg and 300μg. The oxitropium-fenoterol combination had a rapid onset of action, and a greater peak effect was achieved than for oxitropium alone. The main unwanted effect was a mildly unpleasant taste. Anticholinergic effects were not seen in this group of elderly men. Oxitropium bromide therefore is an effective bronchodilator with slow onset but prolonged activity and few side effects when used in patients with moderately severe obstruction of the airways. An appropriate dose appears to be 200μg. Addition of oxitropium to fenoterol appears to offer even greater efficacy.