The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities
- Published
- Accepted
- Subject Areas
- Computational Biology, Pharmacology
- Keywords
- Caco-2 cells, Facilitated diffusion/transport, Permeability, Oral absorption, Transcellular transport, Mathematical models, Transporter-mediated uptake, Cheminformatics, Transporters
- Copyright
- © 2015 O'Hagan et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
- Cite this article
- 2015. The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities. PeerJ PrePrints 3:e1271v1 https://doi.org/10.7287/peerj.preprints.1271v1
Abstract
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 (1310 and 230.10-6 cm.s-1) recently used in some recent 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, log P, 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.
Author Comment
This is a submission to PeerJ for review.
Supplemental Information
Set of Caco-2 permeabilities and RDKit descriptors used herein
Drugs_Caco2_compilation_with_descriptors_2.xls