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 μm or 6 μm; periods 1 and 2). Subjects also received radio-labelled salbutamol using a polydisperse nebuliser (period 3) and unlabelled salbutamol (400 μg) using a polydisperse pressurized metered dose inhaler with volumatic spacer (pMDI; period 4). Results Small monodisperse particles (1.5 μm) achieved significantly better total lung deposition (TLD, mean % ± SD) than larger particles (6 μm), where polydisperse nebulisation was poor; (TLD, 64.93 ± 10.72; 50.46 ± 17.04; 8.19 ± 7.72, respectively). Small monodisperse particles (1.5 μm) achieved significantly better lung penetration (mean % ± SD) than larger particles (6 μm), 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 μm and 6 μm 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.