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

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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.

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Acknowledgment

This study was supported by Janssen Pharmaceutical K.K. and the National Institute of Radiological Sciences. We extend our thanks to Dr. Shoko Nozaki, Dr. Amane Tateno, Dr. Tetsuya Ichimiya, Dr. Koichiro Watanabe, Dr. Kensuke Nomura, Dr. Takashi Nakayama, Mr. Katsuyuki Tanimoto, Mr. Takahiro Shiraishi, Mr. Akira Ando, and Ms. Yoshiko Fukushima for their help with this study.

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Authors and Affiliations

  1. Department of Molecular Neuroimaging, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba, 263-8555, Japan

    Ryosuke Arakawa, Hiroshi Ito, Akihiro Takano, Hidehiko Takahashi, Takuya Morimoto & Tetsuya Suhara

  2. Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan

    Ryosuke Arakawa & Yoshiro Okubo

  3. Asai Hospital, Chiba, Japan

    Takeshi Sassa

  4. Onda-daini Hospital, Chiba, Japan

    Katsuya Ohta

  5. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan

    Motoichiro Kato

Authors
  1. Ryosuke Arakawa
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  2. Hiroshi Ito
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  3. Akihiro Takano
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  4. Hidehiko Takahashi
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  5. Takuya Morimoto
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  6. Takeshi Sassa
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  7. Katsuya Ohta
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  8. Motoichiro Kato
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  9. Yoshiro Okubo
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  10. Tetsuya Suhara
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Correspondence to Tetsuya Suhara.

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Arakawa, R., Ito, H., Takano, A. et al. Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacology 197, 229–235 (2008). https://doi.org/10.1007/s00213-007-1029-z

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  • DOI: https://doi.org/10.1007/s00213-007-1029-z

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