Prediction of pharmacodynamics and plasma levels of enantiomer of antidepressants with population pharmacokinetic analysis

• Project/Area Number: 25461739
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Dokkyo Medical University
• Principal Investigator: SHIMODA KAZUTAKA 獨協医科大学, 医学部, 教授 (30196555)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: mirtazapine / CYP2D6 / pharmacokinetics / pharmacogenetics

Outline of Final Research Achievements

We examined effect of the CYP2D6 genetic polymorphism on pharmacokinetics of mirtazapine (MIR) associated with the metabolism of MIR. Plasma levels of S-(+)-MIR, R-(-)-MIR, S-(+)-desmethylmirtazapine (DMIR) and R-(-)-DMIR were measured. The individual having a homozygote of CYP2D6 *10 was found to show significantly high blood level as compared with the individual which did not have CYP2D6*10. Plasma levels of conjugated metabolites of S-(+)-MIR, R-(-)-MIR, S-(+)-MIR;DMIR and R-(-)-DMIR were found to be as approximately 10 times high as those of non-conjugated compound.

Research Products

• [Journal Article] Factors Affecting Steady-state Plasma Concentrations of Enantiomeric Mirtazapine and its Desmethylated Metabolites in Japanese Psychiatric Patients. (2015)
  • Author(s): Hayashi Y, Watanabe T, Aoki A, Ishiguro S, Ueda M, Akiyama K, Kato K, Inoue Y, Tsuchimine S, Yasui-Furukori N, Shimoda K.
  • Journal Title: Pharmacopsychiatry Volume: 48 Issue: 07 Pages: 279-85
  • DOI: 10.1055/s-0035-1565069
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Imapct of CYP2D6*10 polymoorphism on thepharmacokinetics of mirtazapine and its desmethylated metabolite in Japanese psychiatric patients treated with mirtazapine (2015)
  • Author(s): T. Watanabe, Y. Hayashi, A. Aoki, S. Ishiguro, M. Ueda, K. Akiyama, K. Kato, Y. Inoue, S. Tsuchimine, N. Yasui-Furukori, K. Shimoda.
  • Journal Title: Clinical Neuropsychopharmacologyand Therapeutics Volume: 6 Pages: 5-15
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] CYP2D6*10遺伝子多型が日本人患者のmirtazapine代謝に与える影響 (2015)
  • Author(s): 渡邊 崇、林 有希、青木顕子、石黒 慎、上田幹人、秋山一文、加藤和子、井上義政、土嶺章子、古郡規雄、下田和孝
  • Organizer: 第28回日本臨床精神神経薬理学会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-29
• [Presentation] 8-OH-ミルタザピン分析を含めたミルタザピン薬物動態学的研究 (2015)
  • Author(s): 林 有希、渡邊 崇、Pierce Jason、青木顕子、石黒 慎、上田幹人、秋山一文、加藤和子、井上義政、土嶺章子、古郡規雄、下田和孝
  • Organizer: 第28回日本臨床精神神経薬理学会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-29
• [Presentation] Effect of CYP2D6*10 polymorphism on mirtazaoine metabolism in Japanese psychiatric patients. (2014)
  • Author(s): T Watanabe, Y Hayashi, A Aoki, S Ishiguro, Y Inoue, K Akiyama, S Tsuchimine, N Yasui-Furukori, K Shimoda
  • Organizer: Europen College of Neuropsychopharmacology
  • Place of Presentation: Berlin
  • Year and Date: 2014-10-18 – 2014-10-21
• [Presentation] Effect of CYP2D6*10 polymorphism on mirtazapine metabolism in Japanese psychiatric patients. (2014)
  • Author(s): T Watanabe, et al
  • Organizer: European College of Neuropsychopharmacology
  • Place of Presentation: Berlin