The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities.

摘要: We bring together fifteen, nonredundant, tabulated collections (amounting to 696 separate measurements) of the apparent permeability (P app) Caco-2 cells marketed drugs. While in some cases there are significant interlaboratory disparities, most quite minor. Most drugs not especially permeable through cells, with median P app value being 16 ⋅ 10(-6) cm s(-1). This is considerably lower than those (1,310 and 230 s(-1)) recently used simulations that purported show values were too great be transporter-mediated only. these outliers, all values, comparatively low normally observed, entirely consistent transporter-only mediated uptake, no need invoke phospholipid bilayer diffusion. The poorly correlated either simple biophysical properties, extent molecular similarity endogenous metabolites (endogenites), or any specific substructural properties. In particular, octanol:water partition coefficient, logP, shows negligible correlation permeability. data best explained on basis enter (and exit) via a multiplicity transporters weak specificity.