The topical study of inhaled drug (salbutamol) delivery in idiopathic pulmonary fibrosis.

ABSTRACT: BACKGROUND:Our aim was to investigate total and regional lung delivery of salbutamol in subjects with idiopathic pulmonary fibrosis (IPF). METHODS:The TOPICAL study was a 4-period, partially-randomised, controlled, crossover study to investigate four aerosolised approaches in IPF subjects. Nine subjects were randomised to receive 99mTechnetium-labelled monodisperse salbutamol (1.5 ?m or 6 ?m; periods 1 and 2). Subjects also received radio-labelled salbutamol using a polydisperse nebuliser (period 3) and unlabelled salbutamol (400 ?g) using a polydisperse pressurized metered dose inhaler with volumatic spacer (pMDI; period 4). RESULTS:Small monodisperse particles (1.5 ?m) achieved significantly better total lung deposition (TLD, mean %?±?SD) than larger particles (6 ?m), where polydisperse nebulisation was poor; (TLD, 64.93?±?10.72; 50.46?±?17.04; 8.19?±?7.72, respectively). Small monodisperse particles (1.5 ?m) achieved significantly better lung penetration (mean %?±?SD) than larger particles (6 ?m), and polydisperse nebulisation showed lung penetration similar to the small particles; PI (mean?±?SD) 0.8?±?0.16, 0.49?±?0.21, and 0.73?±?0.19, respectively. Higher dose-normalised plasma salbutamol levels were observed following monodisperse 1.5 ?m and 6 ?m particles, compared to polydisperse pMDI inhalation, while lowest plasma levels were observed following polydisperse nebulisation. CONCLUSION:Our data is the first systematic investigation of inhaled drug delivery in fibrotic lung disease. We provide evidence that inhaled drugs can be optimised to reach the peripheral areas of the lung where active scarring occurs in IPF. TRIAL REGISTRATION:This trial was registered on clinicaltrials.gov ( NCT01457261 ).

SUBMITTER: Usmani OS 

PROVIDER: S-EPMC5801831 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature