Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1016/j.ejps.2025.107280 |
Licence  |
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| Title (Primary) | Predicting Caco-2/MDCK intrinsic membrane permeability from HDM-PAMPA-Derived hexadecane/water partition coefficients |
| Author | Dahley, C.; Goss, K.-U.; Ebert, A.
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| Source Titel | European Journal of Pharmaceutical Sciences |
| Year | 2025 |
| Department | COMPBC |
| Page From | art. 107280 |
| Language | englisch |
| Topic | T9 Healthy Planet |
| Supplements | https://ars.els-cdn.com/content/image/1-s2.0-S0928098725002787-mmc1.pdf https://ars.els-cdn.com/content/image/1-s2.0-S0928098725002787-mmc2.xlsx |
| Keywords | HDM-PAMPA; hexadecane/water partition coefficient; Caco-2; MDCK; intrinsic membrane permeability; solubility-diffusion model |
| Abstract | Reliable
membrane permeability data are essential in early drug development.
Therefore, there is a strong need for robust experimental
high-throughput screening methods, or ideally, accurate predictive
tools, to assess membrane permeability. In a previous study, we
demonstrated that the solubility-diffusion model can successfully
predict passive permeability across biological Caco-2 and MDCK
membranes, provided accurate hexadecane/water partition coefficients (Khex/w) are available. In this study, we investigated the HDM-PAMPA method for determining Khex/w. We measured our own data (64 compounds) using this assay and compared the results with established methods such as black lipid membrane (BLM) experiments and classical two-phase systems. Our results show good agreement across methods, with both our data and literature values aligning closely. Using these experimentally determined Khex/w values, we achieved accurate predictions of permeability in Caco-2 and MDCK cell membranes (RMSE = 0.8, n = 29) based on a previously calibrated equation. We further evaluated the in silico prediction of Khex/w using the UFZ-LSER database and the software COSMOtherm. COSMOtherm performed nearly as well as experimental measurements (RMSE = 1.20, n = 29), while the LSER approach (RMSE = 1.63, n = 29) is best applied when experimental descriptors are available or as a complement to COSMOtherm. This work highlights the practical utility of Khex/w in high-throughput permeability estimation, which can support efficient screening and prioritization of drug candidates in pharmaceutical research. |
| Persistent UFZ Identifier | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=31337 |
| Dahley, C., Goss, K.-U., Ebert, A. (2025): Predicting Caco-2/MDCK intrinsic membrane permeability from HDM-PAMPA-Derived hexadecane/water partition coefficients Eur. J. Pharm. Sci. , art. 107280 10.1016/j.ejps.2025.107280 |
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