A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture

Bosquillon, Cynthia and Madlova, Michaela and Patel, Nilesh and Clear, Nicola and Forbes, Ben (2017) A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture. Pharmaceutical Research . ISSN 1573-904X

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Abstract

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.

Item Type: Article
Keywords: 16HBE14o-; biopharmaceutics; calu-3; inhalation; isolated perfused lungs (IPL); NHBE permeability; pulmonary
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: 10.1007/s11095-017-2251-y
Depositing User: Eprints, Support
Date Deposited: 25 Sep 2017 14:29
Last Modified: 14 Oct 2017 08:41
URI: http://eprints.nottingham.ac.uk/id/eprint/46718

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