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

Research Project

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 *help	¥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 2D610 was found to show significantly high blood level as compared with the individual which did not have CYP2D610. 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.