Dopamine D_2/3 occupancy of ziprasidone across a day: A within-subject PET study

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 D_2/3 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 D_2/3 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 % D_2/3 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 D_2/3 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 D_2/3 receptor occupancy (i.e. 60 %). Clinical Trials Registration: 24-Hour Time Course of Striatal Dopamine D ₂ Receptor Occupancy of Ziprasidone: A PET Study, www.clinicaltrials.gov/ct2/show/NCT00818298, NCT00818298