What is a P-gp inhibitor?

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 happens when P-gp is inhibited?

Like the enzymes involved in drug metabolism, substrates of P-glycoprotein can potentially act as inhibitors or inducers of its function. Inhibition of P-glycoprotein can result in increased bioavailability of the susceptible drug. Induction of P-glycoprotein reduces the bioavailability.

What drugs are P-gp substrates?

Examples of drugs that are substrates of P-gp efflux pump include: Apixaban, colchicine, cyclosporine, dabigatran, digoxin, edoxaban, rivaroxaban, and tacrolimus. The degree of effect on P-gp substrate serum concentration may be altered by dose and timing of orally administered P-gp inhibitor or inducer.

Is digoxin a P-gp substrate?

Digoxin is certainly a sensitive probe substrate of P-gp in in vitro studies, as evidenced by a high efflux ratio across Caco-2, MDR1-MDCK and MDR1-LLCPK1 cells, as well as effective inhibition of efflux in the presence of P-gp inhibitors.

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 azithromycin a P-gp inhibitor?

The FDA approved macrolide antibiotics (erythromycin, azithromycin, and clarithromycin) were all reported as p-gp inhibitors.

Is digoxin a P-gp inhibitor?

Conclusions—Quinidine and digoxin are both substrates for P-glycoprotein, and quinidine is a potent inhibitor of digoxin transport in vitro.

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-gp activity?

P-glycoprotein (P-gp) is a transmembrane drug efflux pump encoded by the MDR-1 gene in humans. Most likely P-gp protects organs against endogenous and exogenous toxins by extruding toxic compounds such as chemotherapeutics and other drugs.

What are CYP3A4 inhibitors?

Potent inhibitors of CYP3A4 include clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit. Inducers of CYP3A4 include phenobarbital, phenytoin, rifampicin, St. John’s Wort and glucocorticoids.

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 …

What is the role of P-glycoprotein 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.