FIGURE 7.

Fitted values of k₂₁T(0) for 50–100 μM amprenavir, (•), and predicted from simulated “model data” (solid line). Model data were simulated for the Michaelis-Menten reaction model for P-gp, without experimental error, using the parameters given in Table 4 for amprenavir. At each concentration, a predicted k₂₁T(0) is found, just like in Fig. 6. The solid hyperbolic line is the predicted k₂₁T(0) for all the model data. At high substrate concentrations, the k₂₁T(0) used to simulate the model data was recovered. However, at low concentrations, the predicted k₂₁T(0) was smaller than the correct value. The k₂₁T(0) values predicted for each concentration of the amprenavir data are shown by solid circles. For each concentration, the best 300 fits gave the same value for k₂₁T(0), i.e., the standard deviation for each point is much smaller than the size of the symbols. The average of the higher amprenavir concentrations was roughly k₂₁T(0) = 0.009 M/s, which is the value shown in Tables 2 and 4 as k₂₁T(0) = 180 (1/s) × 50 (μM) = 0.009 M/s. Thus, for all subsequent fittings for amprenavir, for each value of T(0) tested, we fixed the value of k₂₁= (0.009 M/s)/T(0).