Fig. 1.
Visual representation of a mechanistic two-compartmental transporter model. The movement of DCF-AG in the proposed model is described by three vectorial processes: 1) Pdif,in, passive diffusion from the buffer into the cell; 2) Kactive, active transport from the buffer into the cell; and 3) Pdif,out, passive diffusion from the cell into the buffer. Active transport for this model applies for the OATP2B1-mediated uptake of DCF-AG. Using differential equations within Berkeley Madonna software, the mass transfer of DCF-AG into and out of each compartment is modeled over time using in vitro time-course data to derive kinetic parameters such as Km, Pdif, and Vmax. Pdif reflects passive diffusion while Km and Vmax are used to characterize active uptake that adheres to Michaelis-Menten kinetics. Kinetic parameterization was performed for uptake at pH 6.0 and 7.4 to reflect the physiologic conditions of the intestine and liver, respectively.