Skip to main content

Research Repository

Advanced Search

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

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.

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 http://eprints.nottingham.ac.uk/id/eprint/46718
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

Files


2017 Pharm Res (Bosquillon).pdf (860 Kb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





You might also like



Downloadable Citations