Table 2.

Pharmacokinetic model variables for the rat and human temozolomide brain disposition models

Variable symbol (units)DefinitionValue*
Rat modelHuman model
Species-dependent pharmacokinetic variables
    K01 (h−1)Elimination rate constant from central compartment0.776 ± 0.0510.333
    V (mL)Volume of distribution233 ± 68.330,300
    PAcsf (mL/h)Permeability-area product in CSF0.283 ± 0.173175
    CLcsf (mL/h)Clearance from CSF0.756 ± 0.313529
Species-independent pharmacokinetic variables
    Knbvev (h−1)Vascular to extravascular influx rate constant in normal brain106 ± 76.9106
    Knbevv (h−1)Extravascular to vascular efflux rate constant in normal brain7.56 ± 5.487.56
    Kbtvev (h−1)Vascular to extravascular influx rate constant in brain tumor81.3 ± 12581.3
    Kbtevv (h−1)Extravascular to vascular efflux rate constant in brain tumor14.9 ± 13.214.9
Physiologic and anatomic variables from the literature
    fuUnbound fraction in plasma0.800.86
    Qcsf (mL/h)Bulk flow rate from CSF0.13230
    Vcsf (mL)Volume of the CSF compartment0.2140
    Qnb (mL/h)Normal brain blood flow99.742,000
    fBvnbNormal brain fractional blood volume0.020.02
    Vnb (mL)Normal brain total volume1.1461,450
    Qbt (mL/h)Brain tumor blood flow3.862,400
    fBvbtBrain tumor fractional blood volume0.050.05
    Vbt (mL)Brain tumor total volume0.11950
  • * Values estimated by maximum likelihood optimization were reported as mean ± SD; all other variables were fixed.