Lipophilic drug absorption systems

Theory and computational aspects of intestinal permeability have been reviewed in detail by Egan and Lauri [27], Briefly, a drug must be somewhat permeable through the membrane of the intestinal tract if it is to be administered orally and achieve systemic exposure. The rate of membrane permeability is strongly related to the lipophilicity and hydrophilicity of the molecule. Thus, models with a small number of descriptors related to those two properties can provide useful predictions of drug absorption. 

Beside membrane transporters such as PepTl and PepT2, which act as absorptive systems, there are transporters like P-gp and the MRP 15, which transport certain drugs actively back into the intestinal lumen. These efflux pumps are located in several tissues including liver, kidney, brain, and intestine [90,91]. In the intestine, efflux systems are predominantly located at the apical side of the epithelial cells. Lipophilic drugs are usually absorbed by the transcellular route so that they are mostly affected by these systems. Interestingly, the intracellular occurring CYP3A metabolizes compounds to substrates that are eliminated by P-gp [92],... 

The new cyclosporine formulation (Sandimmun Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ) is a self-microemulsifying drug delivery system, which consists of the drug in a lipophilic solvent (corn oil), hydrophilic cosolvent (propylene glycol) surfactant and an antioxidant [37]. Upon contact with GI fluids, Sandimmun Neoral readily forms a homogenous, monophasic microemulsion, which allows the absorption of the drug molecules. Unlike Sandimmun, the formation of this microemulsion is independent of bile salt activity, and indeed, studies have shown that the absorption of cyclosporine from the new formulation is much less dependent on bile flow [38] and is unaffected by food intake [39],... 

After absorption, most drugs and xenobiotics traverse the enterocyte and are absorbed into the portal blood. A small number of highly lipophilic drugs, however, are transported to the systemic circulation by means of the intestinal lymphatics. 

N. H. Shah, M. T. Carvajal, C. I. Patel, M. H. Infeld, and A. W. Malick, Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs, Int. J. Pharmaceut. 106 15-23 (1994). 

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