Lung deposition of inhaled once-daily long-acting muscarinic antagonists standard jet nebulizer or dry powder inhaler, measured using functional respiratory imaging, in patients with chronic obstructive pulmonary disease.

BACKGROUND

Data for bronchodilator deposition nebulizers and dry powder inhalers (DPIs) in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD) are limited. We used functional respiratory imaging (FRI) to determine deposition patterns for revefenacin solution a PARI LC Sprint nebulizer and tiotropium powder HandiHaler DPI.

METHODS

Ten patients with COPD, of whom 9 had severe airflow obstruction, were selected from FLUIDDA's database. The study did not enroll patients. Drug deposition in the extrathoracic and intrathoracic regions, including the central and peripheral airways was simulated by FRI. The percentage of delivered dose and central-to-peripheral (C/P) deposition ratio for nebulizer and DPI were evaluated.

RESULTS

Mean ± standard deviation (SD) age was 64.7 ± 7.1 years, height was 168.8 ± 8.5 cm, and percent predicted forced expiratory volume in 1 s was 40.8 ± 12.3%; 50% of patients were men. At optimal inhalation flow, intrathoracic and peripheral deposition was three-fold higher for revefenacin nebulizer than tiotropium HandiHaler (mean ± SD 34.6 ± 8.53% 10.9 ± 5.67% and 18.2 ± 4.30% 5.8 ± 2.73% of delivered dose, respectively). Similar results were observed for suboptimal flow (mean ± SD percentage of revefenacin tiotropium: intrathoracic, 32.1 ± 8.3% 15.1 ± 5.9%; peripheral; 16.6 ± 4.1% 8.4 ± 2.9%). The C/P deposition ratio for nebulizer was similar to DPI (mean ± SD 0.915 ± 0.241 0.812 ± 0.249 at optimal; 0.947 ± 0.253 0.784 ± 0.219 at suboptimal flow), even though the mass median aerodynamic diameter of revefenacin was higher than tiotropium. C/P deposition ratio for revefenacin decreased after bronchodilation (0.915 ± 0.241 pre-bronchodilation 0.799 ± 0.192 post-bronchodilation), suggesting progressively better deposition in the peripheral region, assuming bronchodilation occurred during the nebulization process.

CONCLUSIONS

These results demonstrate more efficient intrathoracic and peripheral deposition for revefenacin standard jet nebulizer than tiotropium HandiHaler, with similar C/P deposition ratio in patients with COPD. Nebulizers are an efficient alternative to DPIs for bronchodilator administration in patients with COPD.