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Background  Effective bronchodilator therapy depends upon adequate drug deposition in the lung. COPD patients who are unable to administer medications efficiently with conventional inhalers may benefit from the use of a nebulizer device. The aim of this study was to evaluate the systemic bioavailability and bronchodilator response of glycopyrronium bromide (GLY) administered by a novel nebulizer (eFlow® closed system [CS] vibrating membrane nebulizer) or dry powder inhaler (DPI) in subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD).    Methods  In this randomized, open-label, single-dose, five-way crossover study, subjects received a sequence of either 50 μg GLY delivered by eFlow CS nebulizer (GLY/eFlow) or 63 μg GLY delivered by DPI (GLY/DPI), with and without activated charcoal, followed by intravenous infusion of 50 μg GLY with a washout period of 7 days between doses. Endpoints included plasma pharmacokinetics, safety and efficacy.    Results  The mean (± SD) baseline predicted forced expiratory volume in 1 s (FEV 1 ) of the 30 subjects who completed the study was 51 ± 15%, with a FEV 1 /forced vital capacity ratio of 50 ± 11%. Without charcoal, the absolute systemic bioavailability of GLY/eFlow and GLY/DPI were approximately 15 and 22%, respectively. Changes from baseline in FEV 1  at 60 min post-dose, without administration of charcoal, were 0.180 L and 0.220 L for GLY/eFlow and GLY/DPI, respectively; FEV 1  improvements were similar when charcoal was administered (0.220 L for both GLY/eFlow and GLY/DPI). There were no significant differences in spirometry between the two devices. Fewer subjects administered GLY/eFlow reported adverse events ( n  = 15) than GLY/DPI ( n  = 18).    Conclusions  After single doses, GLY/DPI delivered numerically higher peak and steady state levels of drug than did GLY/eFlow. Nebulized GLY produced similar bronchodilation but lower systemic levels of drug than GLY/DPI. Slightly higher number of subjects reported adverse events with GLY/DPI than with GLY/eFlow. Nebulized GLY may offer an effective alternative to patients with COPD not adequately treated with other devices.    Trial registration   NCT02512302  (ClinicalTrials.gov). Registered 28 May 2015.    Electronic supplementary material  The online version of this article (10.1186/s12931-019-1113-z) contains supplementary material, which is available to authorized users.

respiratory research

Evaluation of systemic absorption and bronchodilator effect of glycopyrronium bromide delivered by nebulizer or a dry powder inhaler in subjects with chronic obstructive pulmonary disease