The Isolated Perfused Lung for Drug Absorption Studies

Abstract

Over the past 20 years, the isolated perfused lung (IPL) tech-nique has been developed for the evaluation of pulmonary drug absorption and disposition. The procedure for establishing the model requires a skilled operator, a validated technique for intra-tracheal drug delivery and a system for maintenance and monitoring of the preparation. Most absorption studies to date have utilised the ex vivo rat lung maintained by ventilation and perfusion in an artificial thorax. Techniques for delivery of drugs into the airspaces of the IPL have been developed and the drug transfer (air-to-perfusate) profiles of a variety of actively and passively transported compounds have been measured. Recent developments include the reporting of in vitro–in vivo correlation for air-to-perfusate transfer in the IPL with pulmonary absorption in the rat in vivo, the use of the IPL to model active transport mechanisms and the use of a human lung reperfusion model. The value of the IPL is in discerning lung-specific drug absorption and disposition kinetics that may be difficult to interpolate from in vivo data and cannot be modelled with physiological relevance using reductive in vitro techniques such as cell culture.