Aerosol Deposition of Inhaled Corticosteroids/Long-Acting β2-Agonists in the Peripheral Airways of Patients with Asthma Using Functional Respiratory Imaging, a Novel Imaging Technology

Abstract

Introduction: Drug deposition in the peripheral airways has been reported to differ between pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). This study was conducted to determine the drug deposition fraction from three inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) combination products for inhalation in the peripheral airways. Methods: An airway deposition model was constructed using computed tomography (CT) images obtained in patients with asthma. Functional respiratory imaging was used to determine the airway deposition of Flutiform® (Kyorin Pharmaceutical), Symbicort® (AstraZeneca and Astellas Pharma), and Relvar® (GlaxoSmithKline K.K.) without actual drug inhalation based on airway images from CT and computational fluid dynamics using drug particle size. Results: The mean drug deposition fractions and standard deviations (SDs) in the peripheral airways for Flutiform, Symbicort, and Relvar were 30.33% ± 1.89%, 18.95% ± 2.03%, and 6.58% ± 0.98% for ICS, and 29.17% ± 1.81%, 17.24% ± 1.87%, and 11.30% ± 1.42% for LABA, respectively, showing that significantly higher proportions of ICS and LABA were deposited to the peripheral airways from Flutiform than from Symbicort and Relvar (p < 0.001). The mean drug deposition fractions and SDs in the entire lung for Flutiform, Symbicort, and Relvar were 46.18% ± 1.29%, 28.85% ± 0.78%, and 13.01% ± 0.66% for ICS, and 44.34% ± 1.23%, 26.32% ± 0.71%, and 20.02% ± 0.80% for LABA, respectively, showing that significantly higher proportions of ICS and LABA were deposited to the lung from Flutiform than from Symbicort and Relvar (p < 0.001). Conclusions: Flutiform (pMDI) was shown to provide significantly higher drug deposition fraction to the central/peripheral airways than Symbicort (DPI) and Relvar (DPI). It is suggested that Flutiform may provide a potent therapeutic option for various asthma patients, including those who have difficulty using DPIs. Trial registration: UMIN000022840. Funding: Kyorin Pharmaceutical Co., Ltd.