Estimation of permeability by passive diffusion through Caco-2 cell monolayers using the drugs' lipophilicity and molecular weight

A recently developed, new theoretical absorption model for passive diffusion through biological membranes describing the dependency of membrane permeability on lipophilicity and molecular size, predicts different sigmoid-hyperbolic permeability-lipophilicity relationships for different molecular weight ranges. This model has been tested with experimental in vitro cultured epithelial cell (Caco-2) permeability data for structurally diverse drugs differing in lipophilicity, ionization state and molecular size. These data were pooled with literature values. Using this simple physicochemical approach, the permeability of a compound through Caco-2 cells by passive diffusion can be predicted from the compounds' distribution coefficient in 1-octanol/water (log D-oct) and its molecular weight (MW). Deviations from this expected behaviour may point to the involvement of biological components in the transport process, which may require further investigations. (C) 1998 Elsevier Science B.V. All rights reserved.