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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

Authors

Cynthia Bosquillon

Michaela Madlova

Nilesh Patel

Nicola Clear

Ben Forbes



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.

Journal Article Type Article
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
APA6 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
DOI https://doi.org/10.1007/s11095-017-2251-y
Keywords 16HBE14o-; biopharmaceutics; calu-3; inhalation; isolated perfused lungs (IPL); NHBE permeability; pulmonary
Publisher URL https://link.springer.com/article/10.1007/s11095-017-2251-y
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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2017 Pharm Res (Bosquillon).pdf (860 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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