| Project/Area Number |
06670960
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
KATO Tadafumi (1996) Shiga University of Medical Science, Department of Psychiatry, Instructor, 医学部, 助手 (30214381)
高橋 三郎 (1994-1995) 滋賀医科大学, 医学部, 教授 (20079916)
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| Co-Investigator(Kenkyū-buntansha) |
MURASHITA Jun Shiga University of Medical Science, Department of Psychiatry, Instructor, 医学部, 助手 (80252386)
ISHIDA Nobuya Shiga University of Medical Science, Department of Psychiatry, Instructor, 医学部, 助手 (20159742)
SHIMODA Kazutaka Shiga University of Medical Science, Department of Psychiatry, Instructor, 医学部, 助手 (30196555)
塩入 俊樹 滋賀医科大学, 医学部, 助手 (40235487)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Treatment-resistant depression / Tricyclic antidepressants / Metabolism / 難治性うつ薬 / 三環系抗うつ病 |
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| Research Abstract |
The aim of this research project is investigating the metabolism of tricyclic antidepressants and probe drug and exploring the biological background of treatment-resistant depression. We measured the concentration in plasma of amitriptyline and its metabolites, nortriptyline and geometric isomers of 10 hydroxynortriptyline and 10-hydroxyamitriptyline in 73 Japanese psychiatric patients receiving amitriptyline. Although there were large interindividual variations in plasma drug concentrations, significant positive correlations were observed between drug concentrations and daily dose of amitriptyline. The metabolic ratios for both hydroxylation and desmethylation varied with 8-to 19 fold interindividual variations.
The clinical significance of monitoring the plasma levels of amitriptyline and its metabolites in prediction of the clinical outcome of depressive episode was investigated in 49 depressive patients. Discriminant analysis of drug concentrations and clinical outcome revealed that
… More
increasing of the plasma levels of amitriptyline and cisisomers of hydroxylated metabolites predicted a better clinical outcome, while increasing of the plasma levels of nortriptyline and trans-isomers of hydroxylated metabolites were shown to predict a poor clinical outcome and clinical outcome of approximately 73% of the subjects could be correctly predicted.
Interethnic differences in plasma concentrations of clomipramine between Japanese and Swedish patients was investigated using therapeutic drug monitoring data. The mean ratio between concentration of C and daily dose in Japanese patients was more than 2 times higher than that of Swedish patients. Oral clearance of C in Japanese was as low as approximately 40% of that of Swedes. These findings suggest that Japanese have a lower clearance of tertiary amine tricyclic antidepressants than Swedes do. Interethnic differences in desmethylation of tertiary amine tricyclic antidepressants might be caused by a lower activity of the cytochrome P450 (CYP) isozymes CYP1A2 and/or CYP2C19 in Japanese compared to Swedes. Less
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