Search for new therapeutic drug candidate by enantiomer pharmacokinetic analysis of mirtazapine

• Project/Area Number: 15K19746
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Dokkyo Medical University
• Principal Investigator: hayashi yuki 獨協医科大学, 医学部, 助教 (70592632)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: mirtazapine / CYP2D6 / pharmacokinetics / pharmacogenetics / enantiomer / グルクロン酸抱合 / エナンチオマー / 遺伝子解析 / 薬物血中濃度

Outline of Final Research Achievements

We examined optical enantiomer plasma concentrations of mirtazapine (MIR) and its metabolites effected factors influencing MIR metabolism including CYP2D6 genetic polymorphism. S-(+)-MIR corrected plasma concentration of smokers was significantly lower than non-smoker group, and individual having homozygotes of CYP 2D6*10 was found to show significantly high blood level as compared with the individual which did not have CYP2D6*10. Multiple regression analysis revealed a significant positive correlation between the number of CYP2D6*10 alleles and corrected plasma concentrations of S-(+)-MIR. We found preliminary results that plasma concentrations of the major conjugated metabolite MIR was extremely low and most of the hydroxylated metabolites was present in the blood as glucuronic acid conjugates.

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
• [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
  • Organizer: 日本臨床精神神経薬理学会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2015-10-29