P-gp pumps

From eq. (2.1) follows for the permissible partial pressure p gp pumped vapor the relation... 

P-glycoprotein (P-gp) works as a transporter at the intestinal mucosa pumping drugs out into the lumen. Absorption of P-gp substrates, such as digoxin, cyclosporine, etc., can be increased by inhibitors of P-gp and reduced by inducers. 

Although nucleoside analogs are not substrates for P-gp or CYP3A4, most protease inhibitors and NNl are substrates for both the P-gp efflux pump (Aungst 1999 ... 

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. 

The use of Caco-2 cell monolayers has gained in popularity as an in vivo human absorption surrogate moreover, the monolayers are generally accepted as a primary absorption screening tool by several pharmaceutical companies [10]. However, Caco-2 cell permeability measurements exhibit certain limitations due to the mechanisms involved. Both passive and active pathways exist active transport tends to increase the absorption across the cells and, since Caco-2 cells overexpress the P-glycoprotein (P-gp) efflux pump, the absorption of some compounds across these cells may be underestimated. 

P-gp is expressed in tumor tissue and serves as a barrier to increased accumulation of cytotoxic anticancer drugs within the cancer cell by actively pumping the drug out of the cell. It is a multidrug resistance element by virtue of the fact that it is promiscuous in terms of substrate selectivity. It, like the cytochromes P450, will accept a wide diversity of structural types. For example, a small sampling of drugs that are substrates for P-gp... 

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