Epithelial permeability and drug absorption in the lungs

Abstract The rate and extent of pulmonary absorption depends on permeability in the airway and alveolar regions of the lungs, plus other factors including the mucosal environment, surface area and perfusion. Most inhaled medicines are for action in the lungs and, unless the target is in the lumen, bioavailability is controlled by epithelial permeability. As drug concentrations in the lungs are very difficult to measure in vivo, clearance of drug from the lungs into the systemic circulation is commonly used as a measure of pulmonary absorption. A number of in vitro, ex vivo and in vivo models are available to measure drug permeability and absorptive clearance from the lungs. Data generated using these models can be used as pulmonary absorption parameters for in silico physiologically-based pharmacokinetic models, and have produced good fits with plasma pharmacokinetics of inhaled medicines in humans.