Physiologically-Based Pharmacokinetic Model to Predict Propellant Levels in Exhaled Air from Pressurized Medical Inhaler Use

Bronchodilator asthma medications, like albuterol, are utilized to treat acute asthmatic exacerbations. They also have been utilized to improve lung function testing and athletic performance in individuals without asthma. These inhaled drugs are commonly administered using pressurized metered dose inhalers (pMDI). Hydrofluorocarbons HFC-134a and HFC-227ea are used as propellants in pMDIs and can be detected in exhaled breath. A physiologically-based pharmacokinetic (PBPK) model was used to simulate inhalation kinetics of the propellants HFC-134a and HFC-227ea, in order to determine the window of detection in exhaled breath for subjects who have inhaled albuterol from a pMDI. The model was developed and validated with data from published studies to predict propellant exhaled breath and venous blood concentrations. The PBPK model was then run to simulate exposure to a single puff from an asthma inhaler using HFC-134a as the propellant, to describe the exposures in a separately reported Air Force Research Laboratory study. On average, the model predicted detection of asthma inhaler use for approximately 16 hours following dosing for an analytical limit of detection (LOD) of 1 part per billion (ppb) or 65 hours post inhalation for a LOD of 1 part per trillion (ppt).