Dopamine D2/3 occupancy of ziprasidone across a day : a within-subject PET study

Abstract

Rationale

Ziprasidone is an atypical antipsychotic recommended to be administered twice daily.

Objectives

The purpose of this study was to investigate whether occupancy of the dopamine D2/3 receptors by ziprasidone is maintained across a day employing a within subject design.

Methods

Positron emission tomography (PET) scans with [11C]-raclopride were performed in 12 patients with schizophrenia while treated with ziprasidone 60 mg twice daily. Each patient completed [11C]-raclopride PET scans at 5, 13 and 23 h after the last dose of ziprasidone. Dopamine D2/3 receptor occupancy was estimated with reference to binding potential data of 44 age- and sex-matched control subjects in the caudate, putamen and ventral striatum.

Results

Eleven scans were available at each time point, and the mean occupancies at 5-, 13- and 23-h scans were 66, 39 and 2 % in the putamen; 62, 35 and −6 % in the caudate; and 68, 47 and 11 % in the ventral striatum, respectively. The time-course of receptor occupancy across the regions indicated an occupancy half-life of 8.3 h. The serum level of ziprasidone associated with 50 % D2/3 receptors occupancy was estimated to be 204 nmol/L (84 ng/ml). Prolactin levels were highest at 5-h post-dose and none showed hyperprolactinemia at 23-h scans.

Conclusions

The absence of ziprasidone striatal D2/3 receptor binding 23 h after taking 60 mg under steady-state conditions is consistent with its peripheral half-life. The results support our earlier report that ziprasidone 60 mg administered twice daily appears to be the minimal dose expected to achieve therapeutic central dopamine D2/3 receptor occupancy (i.e. 60 %).