II. Physiology

  1. P-Glycoprotein (P-gp) is efflux transporter
    1. Transports drugs out of cells and into intestinal lumen, urine or bile
    2. Prevents some agents from crossing the blood-brain barrier
  2. Substrates of P-gp have altered intestinal excretion in the presence of the inducers and inhibitors below
  3. 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
  4. Some P-gp substrates are affected by both P-gp and CYP3A4
    1. Apixiban, Dabigatran, Rivaroxaban should be avoided with Clarithromycin and itraconzaole (strong inhibitors of both P-gp and CYP3A4)
      1. Increased risk of bleeding (due to increased serum levels)
    2. Apixiban, Dabigatran, Rivaroxaban should be avoided with Rifampin, Phenytoin, St Johns Wort (inducers of both P-gp and CYP3A4)
      1. Increased risk of clotting (due to decreased serum levels)
  5. References
    1. (2013) Presc Lett 20(10): 58 [PubMed]

III. Drug Interactions: P-Glycoprotein Substrates

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

  1. Amiodarone
  2. Clarithromycin (strong)
  3. Conivaptan (strong)
  4. Cyclosporine
  5. Dronedarone
  6. Elacridar
  7. Erythromycin
  8. Ketoconazole (strong)
  9. Itraconazole (strong)
  10. Nelfinavir
  11. Quinidine
  12. Reserpine
  13. Ritonavir (strong)
  14. Saquinavir
  15. Tacrolimus
  16. Valspodar
  17. Verapamil
  18. Voriconazole

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

Images: Related links to external sites (from Bing)

Related Studies (from Trip Database) Open in New Window