Metabolism

P-Glycoprotein

P-Glycoprotein, P-Glycoprotein Inhibitor, P-Glycoprotein Substrate, P-Glycoprotein Inducer, P-gp

P-Glycoprotein (P-gp) is efflux transporter
1. Categorized as a Adenosine Triphosphate-binding casette (ABC) drug uptake/efflux transporter
2. Transports drugs out of cells and into intestinal lumen, urine or bile
3. Prevents some agents from crossing the blood-brain barrier
Substrates of P-gp have altered intestinal excretion in the presence of the inducers and inhibitors below
Many Drug Interactions previously attributed to CYP3A4 are due to P-Glycoprotein effects
1. Digoxin is not metabolized by CYP3A4 but it is affected significantly by P-Glycoprotein
2. Digoxin Toxicity is increased with Clarithromycin, Dronedarone, Amiodarone
  1. Decrease oral Digoxin doses by 50% when these P-gp inhibitors are used concurrently
3. Digoxin levels are decreased when used with Rifampin and Phenytoin
  1. Increase oral Digoxin doses by 30% when these P-gp inducers are used concurrently
Some P-gp substrates are affected by both P-gp and CYP3A4
1. Apixaban, Dabigatran, Rivaroxaban should be avoided with Clarithromycin and itraconzaole
  1. Strong inhibitors of both P-gp and CYP3A4
  2. Increased risk of bleeding (due to increased serum levels)
2. Apixaban, Dabigatran, Rivaroxaban should be avoided with Rifampin, Phenytoin, St Johns Wort
  1. Inducers of both P-gp and CYP3A4
  2. Increased risk of clotting (due to decreased serum levels)
References
1. (2013) Presc Lett 20(10): 58 [PubMed]

Drug Interactions
P-Glycoprotein Inhibitors (result in decreased clearance of substrates with risk of toxicity)

Drug Interactions
P-Glycoprotein Inducers (result in increased clearance of substrates with risk of inadequate serum levels)