P-glycoprotein and its role in drug-drug interactions

Abstract

Efflux transporters such as P-glycoprotein play an important role in drug transport in many organs. 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. Many, but not all, of the drugs which are transported by P-glycoprotein are also metabolised by cytochrome P450 3A4. 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.