Ba 679 Br, a new long-acting antimuscarinic bronchodilator: a pilot dose-escalation study in COPD

Preclinical studies with Ba 679 Br have demonstrated a significantly longer duration of action than ipratropium bromide. Following inhalation of single doses, no systemic antimuscarinic effects were noted at doses likely to be bronchodilating in man. The objective of the present pilot-study of Ba 679 Br was to establish the dose-range for its bronchodilatory activity in a small number of chronic obstructive pulmonary disease (COPD) patients, before initiating a formal dose- and time-response study. Employing an open cross-over design, the efficacy of Ba 679 Br was tested, following single inhalational administration of five doses of increasing magnitude on separate days in six patients with COPD. A piezoelectric crystal was used, in order to nebulize an aqueous solution into a mist suitable for inhalation. There was a mean increase in forced expiratory volume in one second (FEV1) of 36% 30 min after inhaling ipratropium bromide 40 micrograms. Pulmonary function tests (FEV1, and specific airways conductance (sGaw)) were performed, at regular time intervals up to 24 h after test drug inhalation. The bronchodilatory activity of Ba 679 Br appeared to be dose-related in the dose-range tested (10-160 micrograms). A peak response was reached in 1.5-2 h, and persisted for 10-15 h in the majority of patients with return to baseline FEV1 approximately 19 h after dosing. No changes in physical examination, electrocardiogram (ECG) and laboratory safety tests from predose values were noted, and no serious adverse events were reported by the patients.(ABSTRACT TRUNCATED AT 250 WORDS)