PREDICTING PULMONARY ABSORPTION OF INHALED DRUGS USING THE EX VIVO ISOLATED PERFUSED LUNG (IPL) MODEL

This study explored the potential of the ex vivo isolated perfused rat lung (IPL) model to predict the lung absorption of inhaled drugs [1]. Unlike in vitro methods, IPL better replicates the physiological environment of the lung, preserving key aspects of lung function and tissue barriers. The focus was on a poorly water-soluble compound in pharmaceutical development, administered in three formulations: freebase powder, compound salt powder, and free-base nanosuspension. The IPL model enabled controlled drug delivery and frequent sampling of the perfusate, facilitating the assessment of pulmonary absorption. This approach aligns with the 3Rs principles by minimizing animal use. The IPL data were compared with in vivo pharmacokinetic profiles from rat studies. Results revealed a strong correlation between ex vivo and in vivo profiles for all formulations, despite differences in the devices used for powder administration in each setting. This study underscores the value of the IPL model in assessing and potentially predicting the pharmacokinetics of inhaled drugs, particularly for poorly water-soluble compounds. Its ability to reduce animal usage and provide frequent sampling makes it a promising tool for preclinical drug development.