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

2017 Fiscal Year Final Research Report

• 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
• Keywords: mirtazapine / CYP2D6 / pharmacokinetics / pharmacogenetics / enantiomer / グルクロン酸抱合

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.

Free Research Field

臨床精神薬理学