What is a P-gp substrate?

P-glycoprotein is one of the drug transporters that determine the uptake and efflux of a range of drugs. This process affects their plasma and tissue concentrations and ultimately their final effects. P-glycoprotein functions as a transmembrane efflux pump, pumping its substrates from inside to outside the cell.

What does P-gp stand for?

permeability glycoprotein
P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) 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 an important protein of the cell membrane that pumps many foreign substances out of cells.

What is the clinical relevance of P-glycoprotein P-gp )?

Because of its expression and localization, it has been suggested that P-gp plays an important role in cancer chemotherapy, intestinal absorption, and brain uptake. This review addresses the significance of the role of P-gp in cancer chemotherapy, drug absorption, and brain uptake.

Is P-glycoprotein the same as MDR1?

MDR1, more commonly referred to as P-gp or P-glycoprotein, is an efflux transporter that serves two major drug transport functions. Firstly, it restricts the distribution of its substrates into organs such as the brain, testes, placenta, and the GIT.

What is the significance of P-glycoprotein in pharmacokinetics?

The general function of P-glycoprotein is now known to protect the body from harmful substances by: Removing drugs absorbed in the intestines back into the gut lumen. Maintaining the integrity of the blood brain barrier. Removing drugs from the kidneys and liver into the urine and bile respectively.

What is P-glycoprotein role in multi drug resistant cancers?

P-glycoprotein (P-gp) is a key player in the multidrug-resistant phenotype in cancer. The protein confers resistance by mediating the ATP-dependent efflux of an astonishing array of anticancer drugs.

What drugs inhibit P-glycoprotein?

Table 1

What anticancer drugs are 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 …

What is a P-gp inhibitor?

Inhibition of P-glycoprotein to prevent drug efflux. P-gp inhibitors are classified into three generations based on their specificity, affinity, and toxicity. First generation inhibitors are pharmacologically active substances which are clinically used for specific treatments but have the ability to inhibit P-gp.

What is P glycoproteins role in multi drug resistant cancers?

What are the substrates of P-gp?

P-gp transports various substrates across the cell membrane including: Drugs such as colchicine, desloratadine, tacrolimus and quinidine. Chemotherapeutic agents such as topoisomerase inhibitors (i.e. etoposide, doxorubicin ), microtubule-targeted drugs (i.e. vinblastine ), and tyrosine kinase inhibitors (i.e. gefitinib, sunitinib ).

Which substrates of P-glycoprotein are susceptible to pharmacokinetics?

Substrates of P-glycoprotein are susceptible to changes in pharmacokinetics due to drug interactions with P-gp inhibitors or inducers. Some of these substrates include colchicine, ciclosporin, dabigatran, digoxin, diltiazem, fexofenadine, indinavir, morphine, and sirolimus.

What is the function of PGP protein?

This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. P-gp is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity.

Where is PGP found in the body?

P-gp is expressed primarily in certain cell types in the liver, pancreas, kidney, colon, and jejunum. P-gp is also found in brain capillary endothelial cells.