Figure 1.
The model has one compartment representing brain (striatum) tissue, which exchanges radiotracer with plasma compartment (volume Vp) with two diffusion constants Kpb and Kbp. In the plasma compartment, cocaine molecules experience an enzymatic Michaelis-Menten elimination, where KM is the Michaelis-Menten constant and Vmax is the maximum velocity of cocaine conversion to the metabolites.
Figure 2.
Modeling of available experimental data (dots) for the concentrations of cocaine in brain (black) and in plasma (red) of human subject.
The experimental data came from reference [37].
Figure 3.
Plots for the cocaine peak concentration (µM) in brain versus the initial concentration (µM) of cocaine in plasma in the presence of a cocaine-metabolizing enzyme (0.035 or 0.5 µM).
Table 1.
Lookup table for the predicted cocaine peak concentration, the peak time (Ptime in min), tb1/2 (in min), and the area under curve (AUC2∞ in human brain for a given initial concentration of cocaine with CocE or CocH or endogenous wtBChE in plasma ([E] = 0.035 µM).
Table 2.
The maximum cocaine plasma concentration, i.e. the value (µM), which a given concentration ([E] = 0.035 or 0.5 µM) of cocaine-metabolizing enzyme (CocE, CocH1, CocH2, or CocH3) can effectively prevent from entering brain and producing physiological effects.
Figure 4.
Comparison between the (+)-cocaine hydrolysis by wide-type BChE and the (−)-cocaine hydrolysis by CocH3.
Upper panel: modeled (−)-cocaine concentration in the brain of human subject with the presence of wild-type BChE or CocH3 in plasma. Lower panel: reported (−)- and (+)-cocaine concentrations in baboon brain (striatum) with the presence of wild-type BChE in plasma; the data from reference [62].