Effect of Propellant on the Pharmacokinetics and Pharmacodynamics of Inhaled Albuterol in Asthmatic Subjects

Hydrofluoroalkane (HFA) propellants have largely replaced chlorofluorocarbon (CFC) propellants in metered dose inhalers (MDI). It is important to document the pharmacokinetics (PK) and pharmacodynamics (PD) of medications delivered using HFA propellants compared to CFC propellants. Six adult asthmatics with mild to moderate asthma were selected for the study. Each subject inhaled 180 μg of albuterol from an MDI with holding chamber. Venous blood was collected for measuring albuterol levels at intervals over 12 h, and spirometric measurements of airflow were measured over the same time period. Plasma samples were analyzed using a GC/MS assay developed in our laboratory. PK and PD parameters were calculated by nonlinear regression using WinNonlin^®. There were no statistically significant differences between PD parameters for HFA versus CFC propellants. The area under the plasma albuterol concentration versus time curve (AUC) was 72% greater for the HFA formulation, indicating a greater lung bioavailability (p = 0.015). This difference in bioavailability did not result in a statistically significant difference in FEV₁ values between the two propellants.