Fig 1.
Concentration versus time curve for E2 and GV models for four VE values at CL of 100 ml/min (left panel) and 40 ml/min (right panel).
Fig 2.
For E2 models for four VE values at CL of 100 ml/min (left panel) and 40 ml/min (right panel), the percentage of terminal apparent volume, percent dose mass in time and half-life of the drug as a function of time.
Dashed horizontal line indicates 95% of final volume.
Fig 3.
For GV models for 4 VE values at CL of 100 ml/min (left panel) and 40 ml/min (right panel), the percentage of terminal apparent volume, percent dose mass in time and half-life of the drug as a function of time.
Dashed horizontal line indicates 95% of final volume.
Table 1.
Time to achieve apparent volume of distribution to 95% of Varea after the intravenous bolus of the drug and terminal half-life of the drug from E2 and GV models.
Table 2.
Pharmacokinetic parameters from the weighted biexponential (E2) and the Tk-GV models.
Comparable measures boxed.
Table 3.
Wilcoxon tests with median parameter comparisons.
Fig 4.
Schematic diagram showing E2 compartmental and GV variable volume models of drug distribution.
The E2 model could also be drawn as a variable volume model in which case a scale factor αexp = VE/Vd(∞) < 1 would define the physical volume at time t to be αexpVd(t). Similarly, for the variable volume adaptively obtained GV model, one can define α = VE/Vd(∞) < 1, and an expanding physical volume αVd(t). Note, both αexp and α are constants at all times for their respective models. The term VSS can be confusing because 1) VSS implies that VE is always a steady state volume, which is not the case as the GV model αVd(t) < VE is concentration depleted at late time, see Eq (30). 2) VSS implies that VE only exists at t = ∞, whereas VE is defined all of the time, i.e., on t = [0,∞) by Eqs (8 & 7). Finally, 3) VSS implies an expected physical volume of distribution for sums of exponential term bolus models, and the apparent volume of distribution for a constant infusion experiment, whereas VE applies to more models as the expected volume of physical distribution of a drug for both the bolus and constant infusion experiments.