Predicting apparent passive permeability of Caco-2 and MDCK cell-monolayers: A mechanistic model.

ABSTRACT: Experimentally derived apparent permeabilities, Papp, through cell monolayers such as Caco-2 and MDCK are considered to be an in-vitro gold standard for assessing the uptake efficiency of drugs. Here, we present a mechanistic model that describes 'passive' Papp values (i.e., neglecting active transport) by accounting for the different resistances solutes encounter when permeating a cell monolayer. We described three parallel permeation pathways, namely a cytosolic-, paracellular-, and lateral route, each of which consists of a number of serial resistances. These resistances were accounted for via a mechanistic depiction of the underlying processes that are largely based on literature work. For the present Papp dataset, about as much chemicals are dominated by the cytosolic route as were do

SUBMITTER: Bittermann K 

PROVIDER: S-EPMC5744993 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature