Gastrointestinal lipophilic drug absorption barriers

Absorption barriers are related to the permeability of drug molecules across the gastrointestinal membrane including the colonic membrane. There are two distinct mechanisms for molecules to cross the membrane via paracellular transport and transcellular transport (Fig. 5). Para-cellular transport involves only passive diffusion where the molecules pass through the tight junctions between the epithelial cells. In contrast, transcellular transport can occur by passive diffusion as well as by active transport, or endocytosis. In general, the hydrophilic molecules diffuse predominantly through the paracellular route, whereas the lipophilic... 

The concept of optimum lipophilicity of a drug for passive transport, e.g. gastrointestinal absorption or transfer through the blood-brain barrier. Nowadays many medicinal chemists are famihar with these relationships and do not any longer realize that much of our knowledge came from such analyses. 

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