The development of models for the evaluation of pulmonary drug disposition

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Introduction: The process of drug disposition in the lung after pulmonary delivery is complex involving absorptive and non-absorptive mechanisms. The lung has also been suggested to be a trapping and metabolizing organ, especially after intravenous administration of drug. A key challenge is to define the most suitable models for the evaluation of pulmonary drug disposition.Areas covered: This review provides an overview of the anatomy and physiology of the lung and sites of action. The authors follow this with a description of the processes associated with pulmonary disposition (deposition, absorption, distribution, metabolism, and non-absorptive clearance). The article also summarizes and compares models and techniques for the assessment of drug disposition in the lung, in terms of characteristic features, advantages and disadvantages. Finally, the authors review pharmaceutical science implications of these findings.Expert opinion: In vivo models are preferred for studying drug deposition, absorption, disposition, and response in the lung. In vitro models may be useful in the initial screening for new compounds and in drug lead optimization. The labor-intensive isolated perfused lung models are most suitable for in-depth studies on drug pulmonary disposition for lead compounds. In the future, engineered lungs may become a more convenient means of evaluating drug disposition in the lung.