|WikiProject Molecular and Cellular Biology||(Rated Start-class, Low-importance)|
Author writes :
"Increased intestinal expression of P-glycoprotein can reduce the absorption of drugs that are substrates for P-glycoprotein. Thus, there is a reduced bioavailability, therapeutic plasma concentrations are not attained. On the other hand, supratherapeutic plasma concentrations and drug toxicity may result because of decreased P-glycoprotein expression Active cellular transport of antineoplastics resulting in multidrug resistance to these drugs"
I'm unclear on this, but if the P-gp is pumping the substance out of the cell, then wouldn't PLASMA concentrations GO UP (not down) ? Eg. would the problem be that there's PLENTY (or too much) medication in the Plasma, and TOO LITTLE in the Target Tissue (eg. inside the cells) ?
Response to the above: No - PGP is expressed on the luminal surface of the intestinal cells (enterocytes). This is the surface that makes contact with the lumen (hollow tube) of the intestine. Drugs try and get into the bloodstream via the enterocytes. However, they have to get past the luminal surface of the enterocytes to do this (tight junctions between the cells prevent drugs squeezing between enterocytes). PGP stops drugs getting into the enterocytes - as soon as they get in, it pumps them back out, into the lumen of the intestine. This means that instead of getting to the plasma, drugs are excreted via the intestine.
There should be relevant material here on the polymorphisms that can inhibit Pgp and cause increases in serum concentration of drugs (i.e digoxin). Not common, but common enough that people should be able to read about it.