Pharmacokinetics and time-course of D2 receptor occupancy induced by atypical antipsychotics in stabilized schizophrenic patients

The 123I-IBZM SPECT measured D2 receptor occupancy (D2RO) in chronically dosed, stabilized schizophrenic patients and its relationship with antipsychotic (AP) pharmacokinetics (PK) over time is still unclear. The aims of this study were: 1) To define the relationship between striatal D2 receptor occupancy (D 2RO) and plasma concentration (CP) in stabilized schizophrenic patients on clinically relevant doses using 123I-IBZM SPECT; 2) To investigate the time course of AP-induced D2RO and corresponding CP. Forty-six schizophrenic patients on their clinically required doses of risperidone, olanzapine, clozapine or quetiapine were included. D 2RO and CP were measured over time following a sparse-sampling experimental design, and individual PK and D2RO-time profiles were estimated using a population approach. Observed striatal D2RO and CP ranges were 28—75% and 9.4—60.5 ng/mL for risperidone, 22—84% and 8.6—89.5 ng/mL for olanzapine, 5—53% and 41.6—818.2 ng/mL for clozapine and 0—64% and 37.9—719.6 ng/mL for qu...