The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities
We bring together fifteen, nonredundant, tabulated collections (amounting to 696 separate measurements) of the apparent permeability (Papp) of Caco-2 cells to marketed drugs. While in some cases there are some significant interlaboratory disparities, most are quite minor. Most drugs are not especial...
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PeerJ Inc.
2015-11-01
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| Series: | PeerJ |
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| Online Access: | https://peerj.com/articles/1405.pdf |
| _version_ | 1797424480681721856 |
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| author | Steve O’Hagan Douglas B. Kell |
| author_facet | Steve O’Hagan Douglas B. Kell |
| author_sort | Steve O’Hagan |
| collection | DOAJ |
| description | We bring together fifteen, nonredundant, tabulated collections (amounting to 696 separate measurements) of the apparent permeability (Papp) of Caco-2 cells to marketed drugs. While in some cases there are some significant interlaboratory disparities, most are quite minor. Most drugs are not especially permeable through Caco-2 cells, with the median Papp value being some 16 ⋅ 10−6 cm s−1. This value is considerably lower than those (1,310 and 230 ⋅ 10−6 cm s−1) recently used in some simulations that purported to show that Papp values were too great to be transporter-mediated only. While these values are outliers, all values, and especially the comparatively low values normally observed, are entirely consistent with transporter-only mediated uptake, with no need to invoke phospholipid bilayer diffusion. The apparent permeability of Caco-2 cells to marketed drugs is poorly correlated with either simple biophysical properties, the extent of molecular similarity to endogenous metabolites (endogenites), or any specific substructural properties. In particular, the octanol:water partition coefficient, logP, shows negligible correlation with Caco-2 permeability. The data are best explained on the basis that most drugs enter (and exit) Caco-2 cells via a multiplicity of transporters of comparatively weak specificity. |
| first_indexed | 2024-03-09T08:01:52Z |
| format | Article |
| id | doaj.art-b06d500887f84583b3ce10775f28569c |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T08:01:52Z |
| publishDate | 2015-11-01 |
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| spelling | doaj.art-b06d500887f84583b3ce10775f28569c2023-12-03T00:40:21ZengPeerJ Inc.PeerJ2167-83592015-11-013e140510.7717/peerj.1405The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similaritiesSteve O’Hagan0Douglas B. Kell1School of Chemistry & The Manchester Institute of Biotechnology and Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), The University of Manchester, Manchester, Lancs, United KingdomSchool of Chemistry & The Manchester Institute of Biotechnology and Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), The University of Manchester, Manchester, Lancs, United KingdomWe bring together fifteen, nonredundant, tabulated collections (amounting to 696 separate measurements) of the apparent permeability (Papp) of Caco-2 cells to marketed drugs. While in some cases there are some significant interlaboratory disparities, most are quite minor. Most drugs are not especially permeable through Caco-2 cells, with the median Papp value being some 16 ⋅ 10−6 cm s−1. This value is considerably lower than those (1,310 and 230 ⋅ 10−6 cm s−1) recently used in some simulations that purported to show that Papp values were too great to be transporter-mediated only. While these values are outliers, all values, and especially the comparatively low values normally observed, are entirely consistent with transporter-only mediated uptake, with no need to invoke phospholipid bilayer diffusion. The apparent permeability of Caco-2 cells to marketed drugs is poorly correlated with either simple biophysical properties, the extent of molecular similarity to endogenous metabolites (endogenites), or any specific substructural properties. In particular, the octanol:water partition coefficient, logP, shows negligible correlation with Caco-2 permeability. The data are best explained on the basis that most drugs enter (and exit) Caco-2 cells via a multiplicity of transporters of comparatively weak specificity.https://peerj.com/articles/1405.pdfCaco-2 cellsFacilitated diffusion/transportPermeabilityOral absorptionTranscellular transportMathematical models |
| spellingShingle | Steve O’Hagan Douglas B. Kell The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities PeerJ Caco-2 cells Facilitated diffusion/transport Permeability Oral absorption Transcellular transport Mathematical models |
| title | The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities |
| title_full | The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities |
| title_fullStr | The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities |
| title_full_unstemmed | The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities |
| title_short | The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities |
| title_sort | apparent permeabilities of caco 2 cells to marketed drugs magnitude and independence from both biophysical properties and endogenite similarities |
| topic | Caco-2 cells Facilitated diffusion/transport Permeability Oral absorption Transcellular transport Mathematical models |
| url | https://peerj.com/articles/1405.pdf |
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