Exploration of enantiomers which is clinically applicable to the pharmacotherapy of depressive disorders by population pharmacokinetic analysis
| Project/Area Number |
17K10280
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
渡邊 崇 獨協医科大学, 医学部, 講師 (10621451)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | pharmacokinetics / pharmacogenetics / enantiomer / venlafaxine / mirtazapine / CYP2D6 / enatiomer / エナンチオマー |
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| Outline of Final Research Achievements |
The pharmacokinetics of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV) were investigated. The correlation coefficients between dose of VEN and plasma concentration of VEN and ODV were 0.57 and 0.94, respectively. Addtionally, the effect of CYP2D6 gene polymorphism on the plasma levels of VEN, ODV and each enantiomer (S-VEN, R-VEN, S-OD, R-ODV) was evaluated. The plasma concentration of each enantiomer was significantly correlated with the dose of VEN. Corrected VEN, ODV, S-ODV, and R-ODV plasma concentrations showed a significant correlation with age. Neither plasma concentration of each enantiomer was significantly associated with the number of CYP2D6*10 alleles.
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| Academic Significance and Societal Importance of the Research Achievements |
現在、モノアミン仮説を凌駕するような革新的な抗うつ薬の開発は停滞しているといって差し支えない。現在使用されているベンラファキシンやミルタザピンのエナンチオマーの薬物動態を解析することによって、新規抗うつ薬の有効性に寄与している物質の同定を行い副作用のリスクが少ない物質を抽出することが期待され、短期間で比較的安全かつ効率的なプロセスで新しい抗うつ薬をうつ病患者に供給することができる可能性が示された。
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Report
(4 results)
Research Products
(17 results)
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[Presentation] 8-Hydroxylation and glucuronidation of mirtazapine in Japanese psychiatric patients: Significance of the glucuronidation pathway of 8-hydroxy-mirtazapine.2019
Author(s)
Masataka Shinozaki, Jason Pierce1, Yuki Hayashi, Takashi Watanabe, Taro Sasaki, Hazuki Komahashi-Sasaki, Kazufumi Akiyama, Kazuko Kato,Yoshimasa Inoue, Shoko Tsuchimine, Norio Yasui-Furukori, Yuji Ozeki, Kazutaka Shimoda
Organizer
The 7th China-Japan joint meeting of basic and clinical pharmacology
Related Report
Int'l Joint Research / Invited
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[Presentation] Early improvement and marriage are determinants of 1-year treatment outcome of paroxetine in outpatients with panic disorder2018
Author(s)
Takashi Watanabe, Mikito Ueda, Shin Ishiguro, Yuki hayashi, Akiko Ariyoshi, Masataka Shinozaki, Kazuko Kato, Kazufumi Akiyama, Kazutaka Shimoda
Organizer
18th World Congress of Basic and Clinical Pharmacology. July 1-6, 2018, Kyoto.
Related Report
Int'l Joint Research
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[Presentation] Pharmacokinetics of mirtazapine included glucuronidated metabolites in Japanese psychiatric patients2017
Author(s)
Takashi Watanabe, Yoshimasa Inoue, Yuki Hayashi, Jason Pierce, Akiko Aoki, Shin Ishiguro, Mikito Ueda, Kazufumi Akiyama, Shoko Tsuchimine, Norio Yasui-Furukori, Kazutaka Shimoda
Organizer
5th Asian College of Neuropsychopharmacology,
Related Report
Int'l Joint Research
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