We assumed that in most practical cases, the plasma concentration-time profile would be obtained before the brain in vivo PK study. Based on this assumption, we first determined the plasma concentration-time profiles for all compounds using compartment models. For each compound, the most suitable basic 1-or 2-compartment model of iv or po administration was applied without a lag time using Phoenix 64, ver. 8.2.2.227 [32] (Figure ). Next, this plasma compartment model was linked to a transit compartment with a velocity constant parameter kin; this transit compartment was adopted to reproduce delayed transition of the compound from the plasma to the brain compartment . This transit compartment was linked to the brain compartment via a velocity constant parameter kin. From the brain compartment, the compound was extruded to the outside of the cell according to the velocity constant parameter, kout.