Drug Transporters: Efflux

Efflux transporters are membrane-bound proteins that pump their substrates out of cells or cellular compartments. Most efflux transporters belong to the ABC superfamily which uses active transport (hydrolysis of ATP) to drive the movement of their substrates across biological membranes. The exceptions to this are MATEs, a subfamily of SLC transporters that use proton gradients to efflux their substrates instead of active transport. While efflux transporters have endogenous substrates, many of them also transport clinically relevant drugs and their metabolites. These transporters are located in multiple organs and tissues including the intestine, liver, kidneys, and blood-tissue barriers. Depending on their localization to either the apical or basolateral membrane of epithelial cells, efflux transporters regulate the movement of drugs into or out of these organs and tissues. Due to their ability to either restrict or facilitate the movement of drugs between systemic circulation and tissues, efflux transporters play important roles in determining drug pharmacokinetics. This article will review the major efflux transporters and their involvement in drug absorption, distribution, and hepatic and renal clearance.