RT Journal Article SR Electronic T1 Predicting Phenolic Acid Absorption in Caco-2 Cells: A Theoretical Permeability Model and Mechanistic Study JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 397 OP 406 DO 10.1124/dmd.111.041665 VO 40 IS 2 A1 Farrell, Tracy L. A1 Poquet, Laure A1 Dew, Tristan P. A1 Barber, Stuart A1 Williamson, Gary YR 2012 UL http://dmd.aspetjournals.org/content/40/2/397.abstract AB There is a considerable need to rationalize the membrane permeability and mechanism of transport for potential nutraceuticals. The aim of this investigation was to develop a theoretical permeability equation, based on a reported descriptive absorption model, enabling calculation of the transcellular component of absorption across Caco-2 monolayers. Published data for Caco-2 permeability of 30 drugs transported by the transcellular route were correlated with the descriptors 1-octanol/water distribution coefficient (log D, pH 7.4) and size, based on molecular mass. Nonlinear regression analysis was used to derive a set of model parameters a′, β′, and b′ with an integrated molecular mass function. The new theoretical transcellular permeability (TTP) model obtained a good fit of the published data (R2 = 0.93) and predicted reasonably well (R2 = 0.86) the experimental apparent permeability coefficient (Papp) for nine non-training set compounds reportedly transported by the transcellular route. For the first time, the TTP model was used to predict the absorption characteristics of six phenolic acids, and this original investigation was supported by in vitro Caco-2 cell mechanistic studies, which suggested that deviation of the Papp value from the predicted transcellular permeability (Papptrans) may be attributed to involvement of active uptake, efflux transporters, or paracellular flux.