Figure 7. Simulated concentration-time curves for the well-stirred tank and flow-limited two-subcompartment model using well-stirred model-optimized and flow-limited two-subcompartment model-calculated partition coefficients for cotinine.

Lower fractional blood volume tissues (adipose, brain, muscle, splanchnic) and higher fractional blood volume tissues (heart, kidney, liver, lung) are simulated (well-stirred tank, solid light gray lines; flow-limited two-subcompartment, dashed dark gray lines) and plotted against rat pharmacokinetic data from Gabrielsson, et al. [27] (filled dark gray circles, mean; vertical bars, range). The well-stirred model is used to optimize cotinine well-stirred partition coefficients, and cotinine biophysical partition coefficients are calculated from optimized well-stirred partition coefficients based on Eq.18 (Table 4). Plasma concentration-time curves are also plotted in each panel (well-stirred, solid light gray lines; flow-limited two-subcompartment, dashed medium gray lines) against rat plasma time course data (filled light gray squares, mean; vertical bars, range). AUC values are reported in Table 5.