P-gp inhibitors enhances the drug level inside cells by inhibiting the efflux.
My specific question is whether a P-gp inhibitor can be used to enhance the level of rifmapicin in lungs and especially macrophages, if the inhibitor (P-gp) lacks the mycobacterial efflux inhibitory and self antimicrobial potential. As some P-gp inhibitors are developed as bioavailability enhancer of anticancer agents.
There is lack of this type of literature.
Rifampicin seems to be a substrate of P-gp, so it is reasonable to think that co-administration of a P-gp inhibitor should increase rifampicin accumulation. Here is a paper that shows enhanced accumulation of rifampicin in mdr knockout mice:
http://www.pnas.org/content/93/9/4001.full.pdf
On the other hand, rifampicin also induces expression of P-gp and some cytochrome P450 enzymes, which could counteract the effect by increasing efflux (if the P-gp inhibitor is not potent enough) and metabolism of the rifampicin.
http://molpharm.aspetjournals.org/content/49/2/311.long
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