FIGURE 7.

Suggested Models illustrating P-gp mechanisms of drug efflux. (A) Classical or pore, (B) flippase and (C) hydrophobic vacuum cleaner models. In the classical model: substrate effluxes out of the cell through a protein channel by interacting with P-gp in the cytoplasm. In the flippase model: substrate transports into the inner leaflet, binds to P-gp (within the membrane), translocates to the outer leaflet, and passively diffuses into the extracellular. In the hydrophobic vacuum cleaner model: the characteristics of ‘pore’ and ‘flippase’ models are mixed (Li et al., 2007).