Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia

Rationale Paliperidone ER is a novel antipsychotic drug in anextended-release (ER) formulation.As with all antipsychotics,careful dose setting is necessary to avoid side effects.Objectives In this study, we measured striatal and extrastriataldopamine D2 receptor occupancy during paliperidoneER treatment in patients with schizophrenia usingpositron emission tomography (PET) to compare regionaloccupancy and to estimate the optimal dose.Materials and methods Thirteen male patients with schizophreniaparticipated in this 6-week multiple-dose study. Sixof them took 3 mg of paliperidone ER per day, four took9 mg, and three took 15 mg. Two to 6 weeks after first drugintake, two PET scans, one with [11C]raclopride and onewith [11C]FLB 457, were performed in each patient on thesame day. The relationship between the dose or plasmaconcentration of paliperidone and dopamine D2 receptoroccupancy was calculated.Results The dopamine D2 receptor occupancies in thestriatum measured with [11C]raclopride and the temporalcortex measured with [11C]FLB 457 were 54.2–85.5% and34.5–87.3%, respectively. ED50 values of the striatum andtemporal cortex were 2.38 and 2.84 mg/day, respectively.There was no significant difference in dopamine D2 receptoroccupancy between the striatum and the temporal cortex.Conclusions The data from this study suggest that paliperidoneER at 6–9 mg provides an estimated level ofdopamine D2 receptor occupancy between 70–80% andthat the magnitude of dopamine D2 receptor occupancy issimilar between the striatum and temporal cortex