TY - JOUR
T1 - Dissociation in Pharmacokinetic Attenuation Between Central Dopamine D2 Receptor Occupancy and Peripheral Blood Concentration of Antipsychotics
T2 - A Systematic Review
AU - Kurose, Shin
AU - Mimura, Yu
AU - Uchida, Hiroyuki
AU - Takahata, Keisuke
AU - Kim, Euitae
AU - Suzuki, Takefumi
AU - Mimura, Masaru
AU - Takeuchi, Hiroyoshi
N1 - Funding Information:
Submitted: October 9, 2019; accepted March 25, 2020. Published online: July 28, 2020. Potential conflicts of interest: Dr Uchida has received grants from Eisai, Meiji Seika, Otsuka, and Sumitomo Dainippon; speaker’s fees from Eli Lilly, Meiji Seika, Merck Sharpe & Dohme (MSD), Otsuka, Pfizer, Sumitomo Dainippon, and Yoshitomi yakuhin; and advisory panel fee from Sumitomo Dainippon. Dr Suzuki has received speaker’s or manuscript fees from Astellas, Eli Lilly, Elsevier, Janssen, Kyowa yakuhin, Meiji Seika, Merck Sharpe & Dohme (MSD), Mitsubishi Tanabe, Novartis, Otsuka, Shionogi, Sumitomo Dainippon, Tsumura, Wiley, and Yoshitomi yakuhin and research grants from Eisai, Meiji Seika, and Mochida. Dr M. Mimura has received speaker’s fees from Daiichi Sankyo, Eisai, Eli Lilly, Fujifilm RI Pharma, Janssen, Merck Sharpe & Dohme (MSD), Mochida, Nippon Chemipher, Novartis, Ono, Otsuka, Pfizer, Sumitomo Dainippon, Takeda, Tsumura, and Yoshitomi yakuhin and research grants from Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Pfizer, Shionogi, Takeda, and Tsumura. Dr Takeuchi has received fellowship grants from Astellas Foundation for Research on Metabolic Disorders, the Canadian Institutes of Health Research (CIHR), Centre for Addiction and Mental Health (CAMH) Foundation, and the Japanese Society of Clinical Neuropsychopharmacology; speaker’s fees from Meiji Seika, Mochida, Otsuka, Sumitomo Dainippon, and Yoshitomi yakuhin; and manuscript fees from Sumitomo Dainippon. Drs Kurose, Y. Mimura, Takahata, and Kim have no competing interests to disclose. Funding/support: This work was partially supported by JSPS KAKENHI Grant Number JP18K15492. Role of the funding source: The funding source had no role in study design, statistical analysis or interpretation of findings, or manuscript preparation or submission for publication. Previous presentation: 31st Collegium Internationale Neuro-Psychopharmacologium; June 18, 2018; Vienna, Austria. Acknowledgments: None. Supplementary material: Available at PSYCHIATRIST.COM.
Publisher Copyright:
© Copyright 2020 Physicians Postgraduate Press, Inc.
PY - 2020/10
Y1 - 2020/10
N2 - Objective: The objective of this study was to examine the extent of possible dissociation in pharmacokinetic decay between central dopamine D2 receptor occupancy with antipsychotics and their peripheral blood concentrations. Data Sources: MEDLINE and Embase were searched using the following keywords : (positron emission tomography OR PET OR single-photon emission computed tomography OR SPECT) AND (dopamine OR D2) AND (receptor* OR occupanc*) AND antipsychotic*, with a limitation of English language (last search: December 14, 2019). Study Selection: The search identified 18 studies that met the following criteria: (1) including patients with schizophrenia spectrum disorders and/or healthy subjects, (2) using positron emission tomography or single-photon emission computed tomography, and (3) examining the time courses of D2 occupancy with antipsychotics and their blood concentrations. Data Extraction: The ratios of D2 occupancy reduction rate (%) from peak to blood concentration reduction rate (%) from peak (relative attenuation ratio) were calculated. Results: Among the studies, oral risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perospirone, haloperidol, sulpiride, and clozapine and long-acting injectable risperidone and haloperidol were included. Relative attenuation ratios were less than 1, indicating a slower central versus peripheral attenuation, across the time points for all antipsychotic types and doses with only a few exceptions. The ratio decreased in a dose-dependent as well as a peak D2 occupancy-dependent fashion. It contrarily increased in a time-dependent manner. Conclusions: The findings indicate pharmacokinetic attenuation of antipsychotics was generally slower at the central versus the peripheral level and pose a critical challenge to the current dosing strategy that primarily relies on peripheral pharmacokinetics of antipsychotics.
AB - Objective: The objective of this study was to examine the extent of possible dissociation in pharmacokinetic decay between central dopamine D2 receptor occupancy with antipsychotics and their peripheral blood concentrations. Data Sources: MEDLINE and Embase were searched using the following keywords : (positron emission tomography OR PET OR single-photon emission computed tomography OR SPECT) AND (dopamine OR D2) AND (receptor* OR occupanc*) AND antipsychotic*, with a limitation of English language (last search: December 14, 2019). Study Selection: The search identified 18 studies that met the following criteria: (1) including patients with schizophrenia spectrum disorders and/or healthy subjects, (2) using positron emission tomography or single-photon emission computed tomography, and (3) examining the time courses of D2 occupancy with antipsychotics and their blood concentrations. Data Extraction: The ratios of D2 occupancy reduction rate (%) from peak to blood concentration reduction rate (%) from peak (relative attenuation ratio) were calculated. Results: Among the studies, oral risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perospirone, haloperidol, sulpiride, and clozapine and long-acting injectable risperidone and haloperidol were included. Relative attenuation ratios were less than 1, indicating a slower central versus peripheral attenuation, across the time points for all antipsychotic types and doses with only a few exceptions. The ratio decreased in a dose-dependent as well as a peak D2 occupancy-dependent fashion. It contrarily increased in a time-dependent manner. Conclusions: The findings indicate pharmacokinetic attenuation of antipsychotics was generally slower at the central versus the peripheral level and pose a critical challenge to the current dosing strategy that primarily relies on peripheral pharmacokinetics of antipsychotics.
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U2 - 10.4088/JCP.19R13113
DO - 10.4088/JCP.19R13113
M3 - Article
C2 - 32726002
AN - SCOPUS:85088879747
SN - 0160-6689
VL - 81
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
IS - 5
M1 - 19r13113
ER -
