24-Hour Time Course of Striatal Dopamine D2 Receptor Occupancy of Ziprasidone: A PET Study
Summary
Ziprasidone is recommended to be dosed twice daily for the treatment of schizophrenia, based on peripheral pharmacokinetics and a knowledge of its half life in plasma level (5-10 hours). However, the plasma kinetics do not always mirror what occurs in the brain. Antipsychotics with a high-affinity at D2 receptors attach for a relatively long time to their binding sites even after plasma levels declined. Based on this observation, another antipsychotic with a similar high-affinity at D2 receptors, ziprasidone, would also be expected to keep a sufficiently high D2 receptor occupancy even 24 hours after the last dose. Given \>60% D2 occupancy is required to maximize chance of therapeutic efficacy, it would be valuable to assess the D2 receptor occupancy 24 hours postdose to predict the therapeutic effects of once-daily regimen. In this study, we will measure D2 receptor occupancy 6, 12, and 24 hours after the last dose of ziprasidone in patients with schizophrenia. The hypotheses are as follows: First, based on the known affinity of ziprasidone, the dopamine D2 occupancy 24 hours after the last administered dose of 80 mg will be \>60%. Second, the difference in dopamine D2 occupancy between scan at 6 hours and 24 hours will be less than 15%. Third, the difference in dopamine D2 occupancy between scan at 12 hours and 24 hours will be less than 10%. Fourth, ED50 24 hours post dose will be higher that those 6 and 12 hours postdose.
Timeline
- Start
- 2009-01
- Primary completion
- 2011-01
- Completion
- 2011-06
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Ziprasidone | Small molecule | 60 mg | — |