Predicting absorption of compounds from an in vivo liver surface based on molecular weight or in vitro release using a dialysis membrane in combination with lipophilicity†

Abstract

A liver surface application (LSA) was developed to reduce the side effects of chemotherapy in liver cancer. The effects of molecular weight (MW) and lipophilicity (log PC) on the absorption of hydrophilic and lipophilic compounds from the rat liver surface were examined. However, how these two factors simultaneously affect compound absorption remains unclear. The combined effects of MW and log PC on the absorption of these compounds in rats and mice were investigated. The compounds were administered to the liver surface using a cylindrical diffusion cell, and in vitro release experiments were conducted using a dialysis membrane to explore the relationship between release and absorption. The results indicate that log (PC/MW^0.5) has a significant linear correlation with log P_{app, absorption} (P_app, apparent permeability coefficient). Similarly, a significant correlation was observed between log (PC × P_{app, release}) and log P_{app, absorption}. These two relationships observed in rats were used to predict compound absorption in mice, and the predicted values closely matched the experimental data. This implies that both combinations of MW and in vitro release with log PC can explain compound absorption from the liver surface. This study provided important information for understanding the absorption characteristics of LSA.