P-glycoprotein

P-glycoprotein designates an ATP-binding cassette transporter protein encoded by the ABCB1 gene, functioning as an efflux pump expressed on cellular membranes that actively transports diverse structurally unrelated compounds out of cells, playing critical roles in drug absorption, distribution, and elimination while contributing to multidrug resistance in cancer. Important expression sites include intestinal epithelium limiting oral absorption, blood-brain barrier restricting central nervous system penetration, and hepatocytes facilitating biliary excretion.

Pharmacological roles include limiting oral absorption, restricting tissue distribution particularly brain penetration, and facilitating elimination. Drug-drug interactions occur when P-glycoprotein inhibitors including verapamil or ritonavir block transporter activity increasing exposure to substrate drugs potentially causing toxicity, while inducers such as rifampicin reduce substrate drug levels causing therapeutic failure. Cancer multidrug resistance develops through P-glycoprotein overexpression in tumour cells, reducing intracellular drug accumulation causing resistance to multiple chemotherapy classes. Drug development employs in vitro assays measuring P-glycoprotein interactions using transfected cell lines, with compounds showing significant efflux requiring further clinical investigation. As understanding deepens regarding transporter structure and substrate recognition, pharmaceutical development increasingly incorporates transporter considerations optimising drug properties.