Psychopharmacology

, Volume 197, Issue 2, pp 229–235

Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia

  • Ryosuke Arakawa
  • Hiroshi Ito
  • Akihiro Takano
  • Hidehiko Takahashi
  • Takuya Morimoto
  • Takeshi Sassa
  • Katsuya Ohta
  • Motoichiro Kato
  • Yoshiro Okubo
  • Tetsuya Suhara
Original Investigation

DOI: 10.1007/s00213-007-1029-z

Cite this article as:
Arakawa, R., Ito, H., Takano, A. et al. Psychopharmacology (2008) 197: 229. doi:10.1007/s00213-007-1029-z

Abstract

Rationale

Paliperidone ER is a novel antipsychotic drug in an extended-release (ER) formulation. As with all antipsychotics, careful dose setting is necessary to avoid side effects.

Objectives

In this study, we measured striatal and extrastriatal dopamine D2 receptor occupancy during paliperidone ER treatment in patients with schizophrenia using positron emission tomography (PET) to compare regional occupancy and to estimate the optimal dose.

Materials and methods

Thirteen male patients with schizophrenia participated in this 6-week multiple-dose study. Six of them took 3 mg of paliperidone ER per day, four took 9 mg, and three took 15 mg. Two to 6 weeks after first drug intake, two PET scans, one with [11C]raclopride and one with [11C]FLB 457, were performed in each patient on the same day. The relationship between the dose or plasma concentration of paliperidone and dopamine D2 receptor occupancy was calculated.

Results

The dopamine D2 receptor occupancies in the striatum measured with [11C]raclopride and the temporal cortex measured with [11C]FLB 457 were 54.2–85.5% and 34.5–87.3%, respectively. ED50 values of the striatum and temporal cortex were 2.38 and 2.84 mg/day, respectively. There was no significant difference in dopamine D2 receptor occupancy between the striatum and the temporal cortex.

Conclusions

The data from this study suggest that paliperidone ER at 6–9 mg provides an estimated level of dopamine D2 receptor occupancy between 70–80% and that the magnitude of dopamine D2 receptor occupancy is similar between the striatum and temporal cortex.

Keywords

Paliperidone ER Dopamine D2 receptor occupancy Striatum Extrastriatum Positron emission tomography Schizophrenia 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Ryosuke Arakawa
    • 1
    • 2
  • Hiroshi Ito
    • 1
  • Akihiro Takano
    • 1
  • Hidehiko Takahashi
    • 1
  • Takuya Morimoto
    • 1
  • Takeshi Sassa
    • 3
  • Katsuya Ohta
    • 4
  • Motoichiro Kato
    • 5
  • Yoshiro Okubo
    • 2
  • Tetsuya Suhara
    • 1
  1. 1.Department of Molecular Neuroimaging, Molecular Imaging CenterNational Institute of Radiological SciencesChibaJapan
  2. 2.Department of NeuropsychiatryNippon Medical SchoolTokyoJapan
  3. 3.Asai HospitalChibaJapan
  4. 4.Onda-daini HospitalChibaJapan
  5. 5.Department of NeuropsychiatryKeio University School of MedicineTokyoJapan

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