A comparison of drug transport in pulmonary absorptionudmodels: isolated perfused rat lungs, respiratory epithelialudcell lines and primary cell culture

摘要

Purpose: To evaluate the ability of human airway epithelialudcell layers and a simple rat isolated perfused lung (IPL) model to predict pulmonary drug absorption in rats in vivo.ududMethod: The permeability of seven compounds selected toudpossess a range of lipophilicity was measured in two airwayudcell lines (Calu-3 and 16HBE14o-), in normal human bronchialudepithelial (NHBE) cells and using a simple isolated perfusedudlungs (IPL) technique. Data from the cell layers andudex vivo lungs were compared to published absorption ratesudfrom rat lungs measured in vivo.ududResults: A strong relationship was observed between the logarithm of the in vivo absorption half-life and the absorption half-life in the IPL (r = 0.97; excluding formoterol). Good log-linear relationships were also found between the apparent first-order absorption rate in vivo and cell layer permeability with correlation coefficients of 0.92, 0.93, 0.91 in Calu-3, 16HBE14o- and NHBE cells, respectively.ududConclusion: The simple IPL technique provided a good prediction of drug absorption from the lungs, making it a useful method for empirical screening of drug absorption in the lungs. Permeability measurements were similar in all the respiratory epithelial cell models evaluated, with Calu-3 having the advantage for routine permeability screening purposes of being readily availability, robust and easy to culture.