Models of deposition, pharmacokinetics, and intersubject variability in respiratory drug delivery

Introduction: Aerosol drug delivery to the lungs via inhalation is widely used in the treatment of respiratory diseases. The deposition pattern of inhaled particles within the airways of the respiratory tract is key in determining the initial delivered dose. Thereafter, dose-dependent processes including drug release or dissolution, clearance, and absorption influence local and systemic exposure to inhaled drugs over time.Areas covered: Empirical correlations, numerical simulation, and in vitro airway geometries that permit improved prediction of extrathoracic and lung deposition fractions in a variety of age groups and breathing conditions are described. Efforts to link deposition models with pharmacokinetic models predicting lung and systemic exposure to inhaled drugs over time are then reviewed. Finally, new methods to predict intersubject variability in extrathoracic deposition, capturing variability in both size and shape of the upper airways, are highlighted.Expert opinion: Recent work has been done to expand in vitro deposition experiments to a wide range of age groups and breathing conditions, to link regional lung deposition models with pharmacokinetic models, and to improve prediction of intersubject variability. These efforts are improving predictive understanding of respiratory drug delivery, and will aid the development of new inhaled drugs and delivery devices.