Pharmacological assessment of the onset of action of aclidinium and glycopyrronium versus tiotropium in COPD patients and human isolated bronchi

Abstract Preclinical studies suggested that aclidinium and glycopyrronium might have a faster onset of action than tiotropium. In this study we assessed the onset of action of aclidinium and glycopyrronium versus tiotropium, all administered at the approved clinical doses, in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and in human isolated bronchi by using different concentrations. Sixteen COPD patients inhaled single doses of aclidinium 400 µg, glycopyrronium 50 μg and tiotropium 18 µg and FEV 1 was measured to assess their onset of action. In human isolated bronchi the time to evoke half maximal relaxation of transmural stimulation was tested from 10 nM to 1 µM for each drug. Nine, eight and twelve patients did not achieve 15% increase of FEV 1 after inhalation of aclidinium, glycopyrronium and tiotropium, respectively. Aclidinium (15.6±7.5 min) and glycopyrronium (17.9±10.4 min) enhanced 15% FEV 1 more rapidly than tiotropium (42.5±19.4 min), with no significant difference ( P >0.05). In isolated airways, glycopyrronium elicited a dose-dependent onset of action (10 nM: 8.2±1.3 min, 100 nM: 7.1±2.1 min, 1 μM: 3.4±0.4 min) that was faster compared to that induced by aclidinium (1 μM: 6.4±0.5 min) and tiotropium (1 μM: 8.4±1.1 min) ( P