Centers for Education &
Research on Therapeutics™
Bauer B, Hartz AM, Fricker G, Miller D. Modulation of p-Glycoprotein Transport Function at the Blood-Brain Barrier. Experimental Biology and Medicine Feb. 2005;230:118-27.
P-Glycoprotein (PGP) Substrates
When researchers started compiling a list of PGP substrates, it became clear that a substantial proportion of known PGP substrates are also subject to metabolic transformation by CYP3A isozymes.1, 2  The overlap in substrate specificity between PGP and CYP3A also extends to similar expression patterns in tissues.  Co-expression of the two in hepatocytes and in the gut wall is of particular importance.  This combination of active efflux via PGP and metabolic biotransformation by CYP3A reduces the oral bioavailability of numerous pharmacologic agents.  Additionally, the potential for augmentation of unwanted drug-drug interactions is possible with this co-expression in barrier tissues.3

1. Kim RB, Wandel C, Leake B et al. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res 1999; 16(3):408-414. 2. Bauer B, Hartz AM, Fricker G, Miller DS. Modulation of p-glycoprotein transport function at the blood-brain barrier. Exp Biol Med (Maywood ) 2005; 230(2):118-127. 3. Callaghan R, Crowley E, Potter S, Kerr ID. P-glycoprotein: so many ways to turn it on. J Clin Pharmacol 2008; 48(3):365-378.