Dopamine D2/3 occupancy of ziprasidone across a day

A within-subject PET study

Takefumi Suzuki, Ariel Graff-Guerrero, Hiroyuki Uchida, Gary Remington, Fernando Caravaggio, Carol Borlido, Bruce Pollock, Benoit Mulsant, Vincenzo Deluca, Zahinoor Ismail, David Mamo

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 %). 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

Original languageEnglish
Pages (from-to)43-51
Number of pages9
JournalPsychopharmacology
Volume228
Issue number1
DOIs
Publication statusPublished - 2013 Jul

Fingerprint

Positron-Emission Tomography
Dopamine
Dopamine D2 Receptors
Raclopride
Corpus Striatum
Putamen
Half-Life
Hyperprolactinemia
ziprasidone
Prolactin
Antipsychotic Agents
Schizophrenia
Clinical Trials
Serum

Keywords

  • C-raclopride
  • Dopamine D receptor
  • Pharmacokinetics
  • Positron Emission Tomography
  • Schizophrenia
  • Ziprasidone

ASJC Scopus subject areas

  • Pharmacology

Cite this

Suzuki, T., Graff-Guerrero, A., Uchida, H., Remington, G., Caravaggio, F., Borlido, C., ... Mamo, D. (2013). Dopamine D2/3 occupancy of ziprasidone across a day: A within-subject PET study. Psychopharmacology, 228(1), 43-51. https://doi.org/10.1007/s00213-013-3012-1

Dopamine D2/3 occupancy of ziprasidone across a day : A within-subject PET study. / Suzuki, Takefumi; Graff-Guerrero, Ariel; Uchida, Hiroyuki; Remington, Gary; Caravaggio, Fernando; Borlido, Carol; Pollock, Bruce; Mulsant, Benoit; Deluca, Vincenzo; Ismail, Zahinoor; Mamo, David.

In: Psychopharmacology, Vol. 228, No. 1, 07.2013, p. 43-51.

Research output: Contribution to journalArticle

Suzuki, T, Graff-Guerrero, A, Uchida, H, Remington, G, Caravaggio, F, Borlido, C, Pollock, B, Mulsant, B, Deluca, V, Ismail, Z & Mamo, D 2013, 'Dopamine D2/3 occupancy of ziprasidone across a day: A within-subject PET study', Psychopharmacology, vol. 228, no. 1, pp. 43-51. https://doi.org/10.1007/s00213-013-3012-1
Suzuki T, Graff-Guerrero A, Uchida H, Remington G, Caravaggio F, Borlido C et al. Dopamine D2/3 occupancy of ziprasidone across a day: A within-subject PET study. Psychopharmacology. 2013 Jul;228(1):43-51. https://doi.org/10.1007/s00213-013-3012-1
Suzuki, Takefumi ; Graff-Guerrero, Ariel ; Uchida, Hiroyuki ; Remington, Gary ; Caravaggio, Fernando ; Borlido, Carol ; Pollock, Bruce ; Mulsant, Benoit ; Deluca, Vincenzo ; Ismail, Zahinoor ; Mamo, David. / Dopamine D2/3 occupancy of ziprasidone across a day : A within-subject PET study. In: Psychopharmacology. 2013 ; Vol. 228, No. 1. pp. 43-51.
@article{3efd4893264a4a7a83cf804fc9181726,
title = "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 {\%}). 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",
keywords = "C-raclopride, Dopamine D receptor, Pharmacokinetics, Positron Emission Tomography, Schizophrenia, Ziprasidone",
author = "Takefumi Suzuki and Ariel Graff-Guerrero and Hiroyuki Uchida and Gary Remington and Fernando Caravaggio and Carol Borlido and Bruce Pollock and Benoit Mulsant and Vincenzo Deluca and Zahinoor Ismail and David Mamo",
year = "2013",
month = "7",
doi = "10.1007/s00213-013-3012-1",
language = "English",
volume = "228",
pages = "43--51",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Dopamine D2/3 occupancy of ziprasidone across a day

T2 - A within-subject PET study

AU - Suzuki, Takefumi

AU - Graff-Guerrero, Ariel

AU - Uchida, Hiroyuki

AU - Remington, Gary

AU - Caravaggio, Fernando

AU - Borlido, Carol

AU - Pollock, Bruce

AU - Mulsant, Benoit

AU - Deluca, Vincenzo

AU - Ismail, Zahinoor

AU - Mamo, David

PY - 2013/7

Y1 - 2013/7

N2 - 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 %). 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

AB - 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 %). 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

KW - C-raclopride

KW - Dopamine D receptor

KW - Pharmacokinetics

KW - Positron Emission Tomography

KW - Schizophrenia

KW - Ziprasidone

UR - http://www.scopus.com/inward/record.url?scp=84879247453&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879247453&partnerID=8YFLogxK

U2 - 10.1007/s00213-013-3012-1

DO - 10.1007/s00213-013-3012-1

M3 - Article

VL - 228

SP - 43

EP - 51

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 1

ER -