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Evaluation of [(11)C]oseltamivir uptake into the brain during immune activation by systemic polyinosine-polycytidylic acid injection: a quantitative PET study using juvenile monkey models of viral infection.
https://repo.qst.go.jp/records/47216
https://repo.qst.go.jp/records/47216eb7746a9-71c1-4140-b64f-c619cc98b220
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-08-06 | |||||
| タイトル | ||||||
| タイトル | Evaluation of [(11)C]oseltamivir uptake into the brain during immune activation by systemic polyinosine-polycytidylic acid injection: a quantitative PET study using juvenile monkey models of viral infection. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Seki, Chie
× Seki, Chie× Oh-Nishi, Arata× Nagai, Yuji× Minamimoto, Takafumi× Obayashi, Shigeru× Higuchi, Makoto× Takei, Makoto× Furutsuka, Kenji× Ito, Takehito× Zhang, Ming-Rong× Ito, Hiroshi× Ito, Mototsugu× Ito, Sumito× Kusuhara, Hiroyuki× Sugiyama, Yuichi× Suhara, Tetsuya× 関 千江× 大西 新× 永井 裕司× 南本 敬史× 大林 茂× 樋口 真人× 武井 誠× 古塚 賢士× 伊藤 岳人× 張 明栄× 伊藤 浩× 須原 哲也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | BACKGROUND: Abnormal behaviors of young patients after taking the anti-influenza agent oseltamivir (Tamiflu®, F. Hoffmann-La Roche, Ltd., Basel, Switzerland) have been suspected as neuropsychiatric adverse events (NPAEs). Immune response to viral infection is suspected to cause elevation of drug concentration in the brain of adolescents. In the present study, the effect of innate immune activation on the brain uptake of [(11)C]oseltamivir was quantitatively evaluated in juvenile monkeys. METHODS:Three 2-year-old monkeys underwent positron emission tomography (PET) scans at baseline and immune-activated conditions. Both scans were conducted under pre-dosing of clinically relevant oseltamivir. The immune activation condition was induced by the intravenous administration of polyinosine-polycytidylic acid (poly I:C). Dynamic [(11)C]oseltamivir PET scan and serial arterial blood sampling were performed to obtain [(11)C]oseltamivir kinetics. Brain uptake of [(11)C]oseltamivr was evaluated by its normalized brain concentration, brain-to-plasma concentration ratio, and plasma-to-brain transfer rate. Plasma pro-inflammatory cytokine levels were also measured. RESULTS: Plasma interleukin-6 was elevated after intravenous administration of poly I:C in all monkeys. Brain radioactivity was uniform both at baseline and under poly I:C treatment. The mean brain concentrations of [(11)C]oseltamivir were 0.0033 and 0.0035% ID/cm(3) × kg, the mean brain-to-plasma concentration ratios were 0.58 and 0.65, and the plasma-to-brain transfer rates were 0.0047 and 0.0051 mL/min/cm(3) for baseline and poly I:C treatment, respectively. Although these parameters were slightly changed by immune activation, the change was not notable. CONCLUSIONS: The brain uptake of [(11)C]oseltamivir was unchanged by poly I:C treatment in juvenile monkeys. This study demonstrated that the innate immune response similar to the immune activation of influenza would not notably change the brain concentration of oseltamivir in juvenile monkeys. |
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| 書誌情報 |
EJNMMI research 巻 24, 号 4, 発行日 2014-07 |
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| 出版者 | ||||||
| 出版者 | Heidelberg: Springer Berlin | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2191-219X | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 25045603 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | doi: 10.1186/s13550-014-0024-8. eCollection 2014. | |||||
