Figure 5. Simulated concentration-time curves using well-stirred and flow-limited two-subcompartment model-optimized partition coefficients for diazepam.
Lower fractional blood volume tissues (adipose, brain, muscle, skin, splanchnic, stomach, and testes), higher fractional blood volume tissues (heart, kidney, liver, lung), and plasma concentration-time curves are simulated using optimized partition coefficients. The well-stirred model is used to optimize diazepam well-stirred partition coefficients, and the flow-limited two-subcompartment model is used to optimize diazepam biophysical partition coefficients (Table 2). Well-stirred tank (solid black lines) and flow-limited two-subcompartment (dashed gray lines) model simulations are plotted against pharmacokinetic data (open circles) in the rat from Gueorguieva et al. [20]. AUC values are reported in Table 3.
