What happens when P-glycoprotein is induced?
In the gut, P-glycoprotein pumps drugs back into the lumen, decreasing their absorption. Drugs which induce P-glycoprotein, such as rifampicin, can reduce the bioavailability of some other drugs. Inhibitors of P-glycoprotein, such as verapamil, increase the bioavailability of susceptible drugs.
How does P-glycoprotein work?
Human P-glycoprotein (ABCB1) is a primary multidrug transporter located in plasma membranes, that, utilizes the energy of ATP hydrolysis to pump toxic xenobiotics out of cells. P-glycoprotein employs a most unusual molecular mechanism to perform this drug transport function.
What does P stand for in P-glycoprotein?
P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is a cell membrane protein that pumps many foreign substances out of cells.
What are CYP3A4 inducers?
Inducers of CYP3A4 include phenobarbital, phenytoin, rifampicin, St. John’s Wort and glucocorticoids.
What do P-glycoprotein inducers do?
An HIV protease inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1 with advanced immunodeficiency. A viral protease inhibitor used in the treatment of HIV infection.
What drugs inhibit P-glycoprotein?
Some common pharmacological inhibitors of P-glycoprotein include: amiodarone, clarithromycin, ciclosporin, colchicine, diltiazem, erythromycin, felodipine, ketoconazole, lansoprazole, omeprazole and other proton-pump inhibitors, nifedipine, paroxetine, reserpine, saquinavir, sertraline, quinidine, tamoxifen, verapamil.
Where is glycoprotein found?
cell membranes
Glycoproteins are found on the surface of the lipid bilayer of cell membranes. Their hydrophilic nature allows them to function in the aqueous environment, where they act in cell-cell recognition and binding of other molecules.
Does azithromycin inhibit P-glycoprotein?
P-gp: P-glycoprotein; US FDA: US Food and Drug Administration….
| Inhibitors of P-gp | |
|---|---|
| Amiodarone | Neratinib |
| Azithromycin (systemic) | Ombitasvir-paritaprevir-ritonavir (Technivie)* |
| Capmatinib | Osimertinib |
| Carvedilol | Propafenone |
Is Gabapentin a CYP3A4 inhibitor?
Valproate is a broad-spectrum inhibitor of UGT enzymes, epoxide hydrolase, and CYP2C enzymes. Felbamate induces CYP3A4, but inhibits CYP2C19 substrates. Topiramate inhibits only CYP2C19 substrates. Ethosuximide, gabapentin, tiagabine, and vigabatrin are neither inducers nor inhibitors of drug metabolism.
What anticancer drugs would be affected by P-glycoprotein?
A plethora of anticancer drugs that are central to many chemotherapeutic regimes are susceptible to P-gp-mediated efflux (Figure 1), such as the microtubule-targeting vinca alkaloids (e.g. vinblastine and vincristine) and taxanes (paclitaxel and docetaxel), the DNA-chelating anthracyclines (doxorubicin and daunorubicin …
How do you inhibit P-glycoprotein?
Examples of drugs that are substrates of P-gp efflux pump include: Apixaban, colchicine, cyclosporine, dabigatran, digoxin, edoxaban, rivaroxaban, and tacrolimus….
| Inhibitors of P-gp | |
|---|---|
| Amiodarone | Neratinib |
| Capmatinib | Osimertinib |
| Carvedilol | Propafenone |
| Clarithromycin | Quinidine |
What is the role of P-glycoprotein in the gut?
Efflux transporters such as P-glycoprotein play an important role in drug transport in many organs. In the gut, P-glycoprotein pumps drugs back into the lumen, decreasing their absorption.
When was the discovery of P-glycoprotein made?
P-gp was first characterized in 1976. P-gp was shown to be responsible for conferring multidrug resistance upon mutant cultured cancer cells that had developed resistance to cytotoxic drugs. The structure of mouse P-gp, which has 87% sequence identity to human P-gp, was resolved by x-ray crystallography in 2009.
Are there any drug interactions with P-glycoprotein?
Dabigatran. As dabigatran etexilate is a substrate of P-glycoprotein, there is potential for drug interactions involving drugs acting on P-glycoprotein. Inhibitors of P-glycoprotein such as ketoconazole, amiodarone, verapamil, ticagrelor and clarithromycin may increase the peak plasma concentrations of dabigatran,…
Is the P-glycoprotein an ABC transporter?
P-gp is a well-characterized ABC-transporter (which transports a wide variety of substrates across extra- and intracellular membranes) of the MDR / TAP subfamily. The normal excretion of xenobiotics back into the gut lumen by P-gp pharmacokinetically reduces the efficacy of some pharmaceutical drugs (which are said to be P-gp substrates).