| Project/Area Number |
10670897
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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 | Niigata University |
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Principal Investigator |
SOMEYA Toshiyuki Department of Psychiatry, Niigata University School of Medicine, Professor, 医学部, 教授 (50187902)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMODA Kazutaka Department of Psychiatry, Shiga University of Medical Science, Instructor, 医学部・附属病院, 講師 (30196555)
MURATAKE Tatsuyuki Department of Psychiatry, Niigata University School of Medicine, Assistant, 医学部, 助手 (60311669)
上原 徹 新潟大学, 医学部, 助手 (60303145)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Refractory Depression / Tricyclic Antidepressants / drug metabolism / CYP2D6 |
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| Research Abstract |
(1) We investigated the impact of genotype of CYP2D6 on steady-state concentrations of nortriptyline (NT) and its metabolites, trans-10-hydroxy-nortriptyline (EHNT) and cis-10-hydroxy-nortriptyline (ZHNT) in 41 Japanese psychiatric population. Significant differences in NT concentrations corrected for dose and weight were observed between the subjects with no mutated allele and the subjects with one mutated allele (no mutated allele vs one mutated allele = 70.3 ± 25.4 (mean ± s.d.) vs 98.4 ± 36.6 ng/ml/mg/kg B.W., p<0.05), and also between the subjects with no mutated allele and two mutated alleles (no mutated allele vs two mutated alleles = 70.3 ± 25.4 vs 147 ± 31.1 ng/ml/mg/kg B.W., p<0.0001). Also significant difference in NT/EHNT, which is representative of the hydroxylation ratio of NT, was observed between the subjects with no mutated allele and the subjects with two mutated alleles (no mutated allele vs two mutated alleles = 0.82 ± 0.30 vs 2.71 ± 0.84, p<0.0001).
(2) We investigated the impact of the genotype of CYP2D6 on the hydroxylation of desipramine in eighteen patients who were administered desipramine hydrochloride per os. Significantly higher plasma concentration of desipramine/daily dose of desipramine/body weight was observed in the subjects with two mutated alleles than in the subjects with either no mutated alleles or one mutated allele (two mutated alleles vs no mutated alleles = 530.4 ± 215.2 vs 118.1 ± 63.9 ng/ml/mg/kg, p<0.001 ; two mutated alleles vs one mutated allele = 530.4 ± 215.2 vs 176.2 ± 62.3 ng/ml/mg/kg, p<0.001). Significantly higher ratio of desipramine/2-hydroxy-desipramine was observed in the subjects with two mutated alleles compared to subjects with no mutated alleles or the subjects with one mutated allele (two mutated alleles versus one mutated allele = 4.39± 0.36 vs 2.00 ± 0.64, p<0.001 ; two mutated alleles vs no mutated alleles = 4.39 ± 0.36 vs 2.02 ± 0.59, p<0.01).
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