Abstract
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 was correlated with the descriptors 1-octanol/ water distribution coefficient (Log D, pH 7.4) and size, based on molecular weight (MW). Non-linear regression analysis was used to derive a set of model parameters a', β' and b' with an integrated molecular weight 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 9 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 6 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.
- absorption
- bioavailability
- cellular transport
- intestinal bioavailability
- intestinal transport
- membrane permeability
- membrane transport
- physiologically-based modeling
- Received July 8, 2011.
- Accepted November 17, 2011.
- The American Society for Pharmacology and Experimental Therapeutics