II. 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)
- Apixaban, Dabigatran, Rivaroxaban should be avoided with Clarithromycin and itraconzaole
- References
III. Drug Interactions: P-Glycoprotein Substrates
IV. 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
- Paliperidone
- Quinidine
- Reserpine
- Risperidone
- Ritonavir (strong)
- Saquinavir
- Tacrolimus
- Valspodar
- Verapamil
- Voriconazole