What does PGP substrate mean?
What does PGP substrate mean?
P-gp is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs.
Is verapamil a PGP substrate?
The cardiovascular drug verapamil is one of the most widely studied Pgp substrates and therefore, represents an ideal drug to investigate the drug-induced ATPase activation of Pgp. As previously noted, verapamil-induced Pgp-mediated ATP hydrolysis kinetics was biphasic at saturating ATP concentrations.
What is P-gp receptor?
We further demonstrate that Pgp is a pattern recognition transporter that shows overlapping substrate specificity with pattern recognition receptors (PRRs) (section The Floppase Model and the Consequences for Drug Pgp Interactions).
How does P-gp affect drug absorption?
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.
Does verapamil inhibit P glycoprotein?
The calcium-channel blocker verapamil is a known inhibitor of P-glycoprotein and may function to block P-glycoprotein-modulated efflux of antiepileptic drugs in the brain, thereby raising the intracellular concentration of antiepileptic drugs and ultimately decreasing seizure burden in patients with refractory epilepsy …
Where is P-gp present?
Pgp is located throughout the human body in organs or tissues with an excretory and/or barrier function, such as liver, kidney, testes and the BBB [4]. At the BBB, Pgp is highly expressed at the vessel walls of the brain capillaries, where it functions as an efflux pump.
How do the 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 are cyp450 substrates?
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.
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 …