Clozapine and risperidone were modeled together with their active metabolites, norclozapine and paliperidone, First, in PK-Sim a rat PBPK model was developed and optimized using literature plasma PK data. 
PK-Sim
Based on the simulated drug and metabolite concentrations in brainECF, drug-D2 receptor binding kinetics (association and dissociation rates) were incorporated in MoBi to predict RO. 
MoBi