What is a substrate of P-glycoprotein?
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What is a substrate of P-glycoprotein?
Important substrates of P-glycoprotein include calcium channel blockers, cyclosporin, dabigatran etexilate, digoxin, erythromycin, loperamide, protease inhibitors and tacrolimus.
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.
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.
What is a drug substrate?
Definitions. substrates are drugs or other substances (xenobiotics) which are metabolized by cytochrome enzymes including 1. pharmacologically active drugs which require metabolism to inactive form for clearance from the body. metabolically activated drugs (prodrugs) which require conversion to active drug.
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 is a p450 substrate?
Is tacrolimus a P-gp inhibitor?
Cyclosporine and tacrolimus are substrates and potent inhibitors of the multidrug transporter, P-glycoprotein, in vitro.
What is MTC and MEC?
The minimum effective concentration (MEC) of a drug is the lowest concentration of the drug required to achieve the therapeutic benefit. On the other hand, the maximum therapeutic concentration or minimum toxic concentration (MTC) is the concentration at which a drug produces unwanted side effects.
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 is a substrate in pharmacology?
substrates are drugs or other substances (xenobiotics) which are metabolized by cytochrome enzymes including 1. pharmacologically active drugs which require metabolism to inactive form for clearance from the body.
What is CYP450 3a4 substrate?
Cytochrome P450 enzymes metabolize approximately 60% of prescribed drugs, with CYP3A4 responsible for about half of this metabolism; substrates include acetaminophen, codeine, ciclosporin (cyclosporin), diazepam, and erythromycin. The enzyme also metabolizes some steroids and carcinogens.
What is P in cytochrome P450?
The name “cytochrome P450 enzymes” is derived due to their several characteristics; they are bound to the membrane of cells (cyto) and contain heme pigment (chrome and P). When bound to carbon monoxide, these proteins produce a spectrum with a wavelength at approximately 450 nm.
