Common questions

What are P-gp substrates?

What are P-gp substrates?

Important substrates of P-glycoprotein include calcium channel blockers, cyclosporin, dabigatran etexilate, digoxin, erythromycin, loperamide, protease inhibitors and tacrolimus. Predicting clinically important interactions is difficult because of interindividual differences in drug transport.

Is tacrolimus a P-gp substrate?

Tacrolimus is a substrate for P-glycoprotein (P-gp), the product of the multidrug resistance (MDR1) gene (1). P-gp acts as a transmembrane efflux pump involved in energy-dependent export of xenobiotics from inside the cells.

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.

How do P-gp inhibitors work?

In general, P-gp can be inhibited by three mechanisms: (i) blocking drug binding site either competitively, non-competitively (Fig. 2) or allosterically; (ii) interfering with ATP hydrolysis; and (iii) altering integrity of cell membrane lipids.

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.

Is atorvastatin a P-gp inhibitor?

Although atorvastatin has been described as an inhibitor of P-gp, higher concentrations are required for maximal P-gp inhibition. Some of the best evidence of P-gp induction has been demonstrated between digoxin and rifampin. Rifampin, a well-known CYP450 inducer, was administered to patients also receiving digoxin.

What is the role of P-gp?

The roles of Pgp in drug disposition include a urinary excretion mechanism in the kidney, a biliary excretion mechanism in the liver, an absorption barrier and determinant of oral bioavailability, and the blood-brain barrier that limits the accumulation of drugs in the brain.

What drugs are P-gp inhibitors?

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.

What drugs inhibit P glycoprotein?

Is grapefruit juice a CYP3A4 inhibitor?

Thus, grapefruit juice appeared to inhibit CYP3A4, an important isozyme of cytochrome P450 since it oxidizes a broad range of drugs and xenobiotics [13], with predominant and perhaps exclusive action on presystemic drug elimination.