FIGURE 1.

Model of a confluent cell monolayer, with the apical membrane on top and the basolateral membrane on the bottom, where it binds to the polycarbonate insert. Passive permeability occurs in both directions. P-gp expressed on the apical membrane transports drug from the inner apical membrane monolayer into the apical chamber. There are two kinetic barriers to transport (see Fig. 3 and accompanying text) flip-flop across the basolateral and apical membranes, with P-gp catalyzing the latter step. The concentration of drug in the apical and basolateral chambers, C_A and C_B, are measured, while the concentration of drug in the inner plasma membrane, C_PC, and the cytosol, C_C, are predicted as part of the data-fitting process.