II. Physiology

  1. 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
  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. Garlic Supplement
  9. Ketoconazole (strong)
  10. Itraconazole (strong)
  11. Nelfinavir
  12. Quinidine
  13. Reserpine
  14. Ritonavir (strong)
  15. Saquinavir
  16. Tacrolimus
  17. Valspodar
  18. Verapamil
  19. 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

Ontology: P-Glycoproteins (C0069906)

Definition (MSH) A subfamily of transmembrane proteins from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS that are closely related in sequence to P-GLYCOPROTEIN. When overexpressed, they function as ATP-dependent efflux pumps able to extrude lipophilic drugs, especially ANTINEOPLASTIC AGENTS, from cells causing multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although P-Glycoproteins share functional similarities to MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS they are two distinct subclasses of ATP-BINDING CASSETTE TRANSPORTERS, and have little sequence homology.
Concepts Biologically Active Substance (T123) , Amino Acid, Peptide, or Protein (T116)
MSH D018435
English P Glycoproteins, P-Glycoproteins, P GLYCOPROTEIN Z, P-Glycoproteins [Chemical/Ingredient], p glycoproteins, p-glycoprotein, p-gp, ATP Binding Cassette, Sub Family B Proteins, ATP-Binding Cassette, Sub-Family B Proteins, Multidrug Resistance Proteins
Swedish P-glykoproteiner
Czech P-glykoproteiny
Finnish P-glykoproteiinit
Russian P-GLIKOPROTEINY, MDRI BELOK, MDRI БЕЛОК, P-ГЛИКОПРОТЕИНЫ
Japanese P-グリコプロテイン類, P-糖蛋白質類
French Protéines de résistance multidrogue, Protéines de résistance multiple aux drogues, Protéines de la sous-famille B à cassette de liaison à l'ATP, Protéines de résistance multiple aux médicaments, Glycoprotéines P
Polish Glikoproteiny P
Croatian P-GLIKOPROTEINI
Portuguese Glicoproteínas-P, Glicoproteínas P, Proteínas de Resistência a Múltiplas Drogas
German P-Glycoproteine, Multidrug-Resistenz-Proteine
Italian P-Glicoproteine
Spanish P-Glicoproteínas, Proteínas Resistentes a Multiples Drogas

Ontology: P-Glycoprotein (C0242643)

Definition (NCI_NCI-GLOSS) A protein that pumps substances out of cells. Cancer cells that have too much p-glycoprotein may not be killed by anticancer drugs.
Definition (NCI) Human p-glycoprotein-1 (1280 aa, 141 kDa) is encoded by the human ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) gene. The protein is an ATP-dependent, transmembrane transport/efflux pump glycoprotein that is expressed in liver, kidney, small intestine and brain.
Definition (MSH) A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).
Definition (CSP) gene product of the multidrug resistance gene mdr-1, believed to be a membrane spanning transporter that can pump a wide variety of cytotoxic agents out of the cell.
Concepts Amino Acid, Peptide, or Protein (T116) , Biologically Active Substance (T123)
MSH D020168
English MDR1 Protein, P Glycoprotein, P-Glycoprotein, P glycoprotein, MDR 001 PROTEIN, MULTIDRUG RESISTANCE PROTEIN 001, P-gp, P-Glycoprotein [Chemical/Ingredient], p-glycoprotein, p glycoprotein, p-gp, glycoprotein p, ATP-Binding Cassette, Sub-Family B, Member 1, Multidrug Resistance Protein 1, PGY 1 Protein, PGY-1 Protein, P-glycoprotein, P-Glycoprotein 1, ABCB1, Multidrug Resistance 1, P-Glycoprotein Transporter
Swedish P-glykoprotein
Czech protein MDR1, P-glykoprotein, protein vícečetné lékové rezistence 1
Finnish P-glykoproteiini
Russian MUL'TILEKARSTVENNYI PERENOSCHIK, P-GLIKOPROTEIN, MDR1 BELOK, MDR1 БЕЛОК, P-ГЛИКОПРОТЕИН, МУЛЬТИЛЕКАРСТВЕННЫЙ ПЕРЕНОСЧИК
Japanese P-糖蛋白, P-糖タンパク質, 多剤輸送体, 糖蛋白質P, MDR1蛋白質, P-糖蛋白質, P糖蛋白質, MDR1タンパク質, P糖タンパク質
French Protéine MDR1, P-gp, Glycoprotéine P
German MDR 001 PROTEIN, MULTIDRUG RESISTENZ PROTEIN 001, MDR1-Protein, P-Glycoprotein, Multidrug-Resistenz-Protein 1
Croatian P-GLIKOPROTEIN
Polish Glikoproteina P, Transporter multileków, Białko MDR1
Spanish Proteína 1 de Resistencia a Multidrogas, P-Glicoproteína, Proteína 1 de Resistencia a Multiples Drogas, Proteína MDR1
Portuguese Glicoproteína-P, Glicoproteína P, Proteína 1 de Resistência a Múltiplas Drogas, Proteína MDR1
Italian P-Glicoproteina