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

• Published in: Respiratory research Vol. 20; no. 1; pp. 132 - 12
• Main Authors: Leaker, Brian R., Singh, Dave, Nicholson, Grant C., Hezelova, Blanka, Goodin, Thomas, Ozol-Godfrey, Ayca, Galluppi, Gerald, Barnes, Peter J.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 28.06.2019; BioMed Central Ltd; BMC
• Subjects: Administration, Inhalation; Adult; Aged; Bioavailability; Bromine compounds; Bronchodilator agents; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - metabolism; Chronic obstructive lung disease; COPD; Cross-Over Studies; Development and progression; Drug Delivery Systems - methods; Drug therapy; Dry Powder Inhalers; Female; Glycine; Glycopyrrolate; Glycopyrrolate - administration & dosage; Glycopyrrolate - metabolism; Glycopyrronium bromide; Humans; Inhalers; Labels; Lung diseases; Lung volume measurement; Male; Medicine; Medicine & Public Health; Middle Aged; Nebulizer; Novels; Patient outcomes; Pneumology/Respiratory System; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - metabolism; Respiratory system agents; Respiratory tract diseases; Spirometry; Testing; Treatment Outcome; United Kingdom; Bioavailability; Nebulizer; Glycopyrronium bromide; COPD
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-019-1113-z

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.