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

Bosquillon, Cynthia; Madlova, Michaela; Patel, Nilesh; Clear, Nicola; Forbes, Ben

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.

Citation

Bosquillon, C., Madlova, M., Patel, N., Clear, N., & Forbes, B. (in press). A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture. Pharmaceutical Research, 34(12), https://doi.org/10.1007/s11095-017-2251-y

• Journal Article Type: Article
• Acceptance Date: Aug 24, 2017
• Online Publication Date: Sep 18, 2017
• Deposit Date: Sep 25, 2017
• Publicly Available Date: Sep 25, 2017
• Journal: Pharmaceutical Research
• Print ISSN: 0724-8741
• Electronic ISSN: 1573-904X
• Publisher: American Association of Pharmaceutical Scientists
• Peer Reviewed: Peer Reviewed
• Volume: 34
• Issue: 12
• DOI: https://doi.org/10.1007/s11095-017-2251-y
• Keywords: 16HBE14o-; biopharmaceutics; calu-3; inhalation; isolated perfused lungs (IPL); NHBE permeability; pulmonary
• Public URL: https://nottingham-repository.worktribe.com/output/883351
• Publisher URL: https://link.springer.com/article/10.1007/s11095-017-2251-y
• Contract Date: Sep 25, 2017