Is verapamil a P-gp inhibitor?
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 …
What is a P-gp inhibitor?
P-gp is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. Chemotherapeutic agents such as topoisomerase inhibitors (i.e. etoposide, doxorubicin), microtubule-targeted drugs (i.e. vinblastine), and tyrosine kinase inhibitors (i.e. gefitinib, sunitinib).
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.
How does P-GP facilitates drug resistance?
P-gp confers resistance by preventing sufficient accumulation of anticancer drugs within the cell, thereby avoiding their cytotoxic or apoptotic effects. This is achieved by its ability to mediate ATP-dependent drug translocation across the plasma membrane against considerable concentration gradients.
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 …
Is azithromycin a P-gp inhibitor?
The FDA approved macrolide antibiotics (erythromycin, azithromycin, and clarithromycin) were all reported as p-gp inhibitors.
Is Amlodipine a P-gp inhibitor?
In addition, amlodipine is also a P-glycoprotein (P-gp) substrate (Darvari and Borou- jerdi, 2004; Harmsze et al., 2010).
What anticancer drugs would be affected by P glycoprotein?
What is the role of P glycoprotein in multi drug resistant cancers?
One important mechanism of MDR involves the multidrug transporter, P-glycoprotein (Pgp), which confers upon cancer cells the ability to resist lethal doses of certain cytotoxic drugs by pumping the drugs out of the cells and thus reducing their cytotoxicity.
Is digoxin a Pgp inhibitor?
Conclusions—Quinidine and digoxin are both substrates for P-glycoprotein, and quinidine is a potent inhibitor of digoxin transport in vitro.