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P-Glycoprotein
Aka: P-Glycoprotein, P-Glycoprotein Inhibitor, P-Glycoprotein Substrate, P-Glycoprotein Inducer, P-gp
- Physiology
- P-Glycoprotein (P-gp) is efflux transporter
- Categorized as a Adenosine triphosphate-binding casette (ABC) drug uptake/efflux transporter
- Transports drugs out of cells and into intestinal lumen, urine or bile
- 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
- Digoxin is not metabolized by CYP3A4 but it is affected significantly by P-Glycoprotein
- Digoxin Toxicity is increased with Clarithromycin, Dronedarone, Amiodarone
- Decrease oral Digoxin doses by 50% when these P-gp inhibitors are used concurrently
- Digoxin levels are decreased when used with Rifampin and Phenytoin
- 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
- Apixaban, Dabigatran, Rivaroxaban should be avoided with Clarithromycin and itraconzaole
- Strong inhibitors of both P-gp and CYP3A4
- Increased risk of bleeding (due to increased serum levels)
- Apixaban, Dabigatran, Rivaroxaban should be avoided with Rifampin, Phenytoin, St Johns Wort
- Inducers of both P-gp and CYP3A4
- Increased risk of clotting (due to decreased serum levels)
- References
- (2013) Presc Lett 20(10): 58 [PubMed]
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Drug Interactions: P-Glycoprotein Substrates
- Apixiban (Eliquis)
- Colchicine
- Cyclosporine
- Dabigatran (Pradaxa)
- Digoxin
- Doxorubicin (Adriamycin)
- Fexofenadine
- Indinavir
- Loperamide
- Morphine
- Quinidine
- Rivaroxaban (Xarelto)
- Rosuvastatin (Crestor)
- Sirolimus
- Tacrolimus (Prograf)
- Talinol
- Verapamil
- Vinblastine
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Drug Interactions: P-Glycoprotein Inhibitors (result in decreased clearance of substrates with risk of toxicity)
- Amiodarone
- Clarithromycin (strong)
- Conivaptan (strong)
- Cyclosporine
- Dronedarone
- Elacridar
- Erythromycin
- Garlic Supplement
- Ketoconazole (strong)
- Itraconazole (strong)
- Nelfinavir
- Quinidine
- Reserpine
- Ritonavir (strong)
- Saquinavir
- Tacrolimus
- Valspodar
- Verapamil
- Voriconazole
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Drug Interactions: P-Glycoprotein Inducers (result in increased clearance of substrates with risk of inadequate serum levels)
- Carbamazepine
- Phenytoin
- Rifampin
- St. John's Wort
- Tipranavir
- Resources
- FDA Drug Interactions
- http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm
- Pharmacy Times
- http://www.pharmacytimes.com/publications/issue/2008/2008-12/2008-12-8474