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