Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays
In this study, Caco-2 permeability results from different laboratories were compared. Six different sets of apparent permeability coefficient (Papp) values reported in the literature were compared to experimental Papp obtained in our laboratory. The differences were assessed by determining the root...
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Elsevier
2017
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| Online Access: | https://eprints.nottingham.ac.uk/39895/ |
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| author | Lee, Jong Bong Zgair, Atheer Taha, Dhiaa A. Zang, Xiaowei Kagan, Leonid Kim, Tae Hwan Kim, Min Gi Yun, Hwi-yeol Fischer, Peter M. Gershkovich, Pavel |
| author_facet | Lee, Jong Bong Zgair, Atheer Taha, Dhiaa A. Zang, Xiaowei Kagan, Leonid Kim, Tae Hwan Kim, Min Gi Yun, Hwi-yeol Fischer, Peter M. Gershkovich, Pavel |
| author_sort | Lee, Jong Bong |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | In this study, Caco-2 permeability results from different laboratories were compared. Six different sets of apparent permeability coefficient (Papp) values reported in the literature were compared to experimental Papp obtained in our laboratory. The differences were assessed by determining the root mean square error (RMSE) values between the datasets, which reached levels as high as 0.581 for the training set compounds, i.e. ten compounds with known effective human permeability (Peff). The consequences of these differences in Papp for prediction of oral drug absorption were demonstrated by introducing the Papp into the absorption and pharmacokinetics simulation software application GastroPlus™ for prediction of the fraction absorbed (Fa) in humans using calibrated “user-defined permeability models”. The RMSE were calculated to assess the differences between the simulated Fa and experimental values reported in the literature. The RMSE for Fa simulated with the permeability model calibrated using experimental Papp from our laboratory was 0.128. When the calibration was performed using Papp from literature datasets, the RMSE values for Fa were higher in all cases except one. This study shows quantitative lab-to-lab variability of Caco-2 permeability results and the potential consequences this can have in the use of these results for predicting intestinal absorption of drugs. |
| first_indexed | 2025-11-14T19:40:04Z |
| format | Article |
| id | nottingham-39895 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:40:04Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-398952020-05-04T19:57:37Z https://eprints.nottingham.ac.uk/39895/ Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays Lee, Jong Bong Zgair, Atheer Taha, Dhiaa A. Zang, Xiaowei Kagan, Leonid Kim, Tae Hwan Kim, Min Gi Yun, Hwi-yeol Fischer, Peter M. Gershkovich, Pavel In this study, Caco-2 permeability results from different laboratories were compared. Six different sets of apparent permeability coefficient (Papp) values reported in the literature were compared to experimental Papp obtained in our laboratory. The differences were assessed by determining the root mean square error (RMSE) values between the datasets, which reached levels as high as 0.581 for the training set compounds, i.e. ten compounds with known effective human permeability (Peff). The consequences of these differences in Papp for prediction of oral drug absorption were demonstrated by introducing the Papp into the absorption and pharmacokinetics simulation software application GastroPlus™ for prediction of the fraction absorbed (Fa) in humans using calibrated “user-defined permeability models”. The RMSE were calculated to assess the differences between the simulated Fa and experimental values reported in the literature. The RMSE for Fa simulated with the permeability model calibrated using experimental Papp from our laboratory was 0.128. When the calibration was performed using Papp from literature datasets, the RMSE values for Fa were higher in all cases except one. This study shows quantitative lab-to-lab variability of Caco-2 permeability results and the potential consequences this can have in the use of these results for predicting intestinal absorption of drugs. Elsevier 2017-05 Article PeerReviewed Lee, Jong Bong, Zgair, Atheer, Taha, Dhiaa A., Zang, Xiaowei, Kagan, Leonid, Kim, Tae Hwan, Kim, Min Gi, Yun, Hwi-yeol, Fischer, Peter M. and Gershkovich, Pavel (2017) Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays. European Journal of Pharmaceutics and Biopharmaceutics, 114 . pp. 38-42. ISSN 1873-3441 Drug permeability; Caco-2 permeability assay; Lab-to-lab variability; Prediction of oral absorption; GastroPlus http://www.sciencedirect.com/science/article/pii/S0939641116305264 doi:10.1016/j.ejpb.2016.12.027 doi:10.1016/j.ejpb.2016.12.027 |
| spellingShingle | Drug permeability; Caco-2 permeability assay; Lab-to-lab variability; Prediction of oral absorption; GastroPlus Lee, Jong Bong Zgair, Atheer Taha, Dhiaa A. Zang, Xiaowei Kagan, Leonid Kim, Tae Hwan Kim, Min Gi Yun, Hwi-yeol Fischer, Peter M. Gershkovich, Pavel Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays |
| title | Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays |
| title_full | Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays |
| title_fullStr | Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays |
| title_full_unstemmed | Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays |
| title_short | Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays |
| title_sort | quantitative analysis of lab-to-lab variability in caco-2 permeability assays |
| topic | Drug permeability; Caco-2 permeability assay; Lab-to-lab variability; Prediction of oral absorption; GastroPlus |
| url | https://eprints.nottingham.ac.uk/39895/ https://eprints.nottingham.ac.uk/39895/ https://eprints.nottingham.ac.uk/39895/ |