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. 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)
  5. References
    1. (2013) Presc Lett 20(10): 58 [PubMed]

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

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

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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