PURPOSE: To evaluate the ability of human airway epithelial cell layers and a simple rat isolated perfused lung (IPL) model to predict pulmonary drug absorption in rats in vivo. METHOD: The permeability of seven compounds selected to possess a range of lipophilicity was measured in two airway cell lines (Calu-3 and 16HBE14o-), in normal human bronchial epithelial (NHBE) cells and using a simple isolated perfused lungs (IPL) technique. Data from the cell layers and ex vivo lungs were compared to published absorption rates from rat lungs measured in vivo. RESULTS: 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. CONCLUSION: 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.

Faculty of Pharmacy Charles University Prague Hradec Kralove Czech Republic

King's College London Pharmaceutical Science Division Franklin Wilkins Building 150 Stamford Street London SE1 9NH UK

Pfizer R and D Sandwich Kent CT13 9NJ UK

School of Pharmacy University of Nottingham Boots Science Building University Park Nottingham NG7 2RD UK

School of Pharmacy University of Reading Whiteknights Reading RG6 6AP UK

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