Drug Absorption Studies Using the Isolated Perfused Lung

Drug Absorption Studies Using the Isolated Perfused Lung 

The following sections provide an overview of the application of the IPL for the study of drug absorption. Examples are provided to illustrate the use of the IPL to study drug permeability, absorption profiles, transport mechanisms and the effects of inhaled dose formulation on drug disposition. 

The earliest studies of solute transfer in the IPL were performed with the aim of measuring the permeability of the lung [156], These studies utilised the simplest form of the IPL in which the lungs can be fluid-filled rather than naturally air-filled, and measured the permeability of the lungs of a variety of species to mannitol and sucrose [156], The permeability of these small hydrophilic compounds in the fluid-filled IPL, which is thought to measure predominately alveolar permeability, was markedly lower than permeability in ex vivo airway tissue. 

Permeability in the IPL has generally been measured by solute flux in the airway to perfusate direction. The flux of solutes in the perfusate to luminal fluid direction compared to absorptive flux [87] revealed a consistent disparity for a series of six hydrophilic compounds, which was suggested to be due to 

An advantage of using the fluid-filled lung is the accuracy of dosimetry and the even distribution of solute throughout the lung. This ensures that permeability is measured across the entire area of the respiratory epithelium. A concern, however, is that the IPL in which the airspaces are flooded with the donor solution may suffer distension of the epithelium leading to increased permeability. 

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