FIGURE 14.

Blowup of the model of an apical membrane showing microvilli, roughly to scale. The figure qualitatively illustrates that the random-walk pathway of drug released at the base of a microvillus will be tortuous, involving many subsequent interactions with the same or a neighboring microvillus and the P-gp they contain. Only the P-gp at the tips of the microvilli can efflux the drug directly into the apical chamber where it can be measured. The hypothesis is that the efflux-active P-gp would be at the top of the microvillus.