title: Dopamine D₂/₃ occupancy of ziprasidone across a day: a within-subject PET study.
abstract: BACKGROUND
  Ziprasidone is an atypical antipsychotic recommended to be administered twice daily.
  
  
  OBJECTIVE
  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 [(11)C]-raclopride were performed in 12 patients with schizophrenia while treated with ziprasidone 60 mg twice daily. Each patient completed [(11)C]-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 %).
  
  
  BACKGROUND
  24-Hour Time Course of Striatal Dopamine D2 Receptor Occupancy of Ziprasidone: A PET Study, www.clinicaltrials.gov/ct2/show/NCT00818298 , NCT00818298.
authors: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors: Takefumi
authors: T
authors: Suzuki
authors: Ariel
authors: A
authors: Graff-Guerrero
authors: Hiroyuki
authors: H
authors: Uchida
authors: Gary
authors: G
authors: Remington
authors: Fernando
authors: F
authors: Caravaggio
authors: Carol
authors: C
authors: Borlido
authors: Bruce
authors: B
authors: Pollock
authors: Benoit
authors: B
authors: Mulsant
authors: Vincenzo
authors: V
authors: Deluca
authors: Zahinoor
authors: Z
authors: Ismail
authors: David
authors: D
authors: Mamo
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D018492:Dopamine Antagonists / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D049268:Positron-Emission Tomography / Q000379:methods; D011388:Prolactin / Q000097:blood; D020891:Raclopride / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy; D013844:Thiazoles / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013997:Time Factors; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013844:Thiazoles; D020891:Raclopride; C092292:ziprasidone; D011388:Prolactin