A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture
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 c...
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| Format: | Article |
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Springer
2017
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| Online Access: | https://eprints.nottingham.ac.uk/46718/ |
| _version_ | 1848797384458371072 |
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| author | Bosquillon, Cynthia Madlova, Michaela Patel, Nilesh Clear, Nicola Forbes, Ben |
| author_facet | Bosquillon, Cynthia Madlova, Michaela Patel, Nilesh Clear, Nicola Forbes, Ben |
| author_sort | Bosquillon, Cynthia |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:03:01Z |
| format | Article |
| id | nottingham-46718 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:03:01Z |
| publishDate | 2017 |
| publisher | Springer |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-467182020-05-04T19:07:27Z https://eprints.nottingham.ac.uk/46718/ 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 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. Springer 2017-09-18 Article PeerReviewed Bosquillon, Cynthia, Madlova, Michaela, Patel, Nilesh, 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, 34 (12). pp. 2532-2540. ISSN 1573-904X 16HBE14o-; biopharmaceutics; calu-3; inhalation; isolated perfused lungs (IPL); NHBE permeability; pulmonary https://link.springer.com/article/10.1007/s11095-017-2251-y doi:10.1007/s11095-017-2251-y doi:10.1007/s11095-017-2251-y |
| spellingShingle | 16HBE14o-; biopharmaceutics; calu-3; inhalation; isolated perfused lungs (IPL); NHBE permeability; pulmonary Bosquillon, Cynthia Madlova, Michaela Patel, Nilesh Clear, Nicola Forbes, Ben A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture |
| title | A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture |
| title_full | A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture |
| title_fullStr | A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture |
| title_full_unstemmed | A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture |
| title_short | A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture |
| title_sort | comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture |
| topic | 16HBE14o-; biopharmaceutics; calu-3; inhalation; isolated perfused lungs (IPL); NHBE permeability; pulmonary |
| url | https://eprints.nottingham.ac.uk/46718/ https://eprints.nottingham.ac.uk/46718/ https://eprints.nottingham.ac.uk/46718/ |