1999 Fiscal Year Final Research Report Summary
Molecular pharmacogenetic study on the marker for drug response in refractory depressive patients
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 |
Section | 一般 |
Research Field |
Psychiatric science
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Research Institution | Niigata University |
Principal Investigator |
SOMEYA Toshiyuki Department of Psychiatry, Niigata University School of Medicine, Professor, 医学部, 教授 (50187902)
|
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)
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Project Period (FY) |
1998 – 1999
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Keywords | Refractory Depression / Tricyclic Antidepressants / drug metabolism / CYP2D6 |
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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[Publications] Morita, S., Shimoda, K., Someya, T., Yoshimura, Y., Kamijima, K. and Kato, N.: "Steady-state plasma levels of nortriptyline and its hydroxylated metabolites in Japanese : The impact of CYP2D6 genotype on the hydroxylation of nortriptyline."J Clin Psychopharmacol. (in press).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Shimoda, K., Morita, S., Hirokane, G., Yokono, A., Someya, T. and Takahashi, S.: "Metabolism of desipramine in Japanese psychiatric patients : The impact of CYP2D6 genotype on the hydroxylation of desipramine."Pharmacol Toxicol. (in press)..
Description
「研究成果報告書概要(欧文)」より
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[Publications] Someya, T., Suzuki, Y., Shimoda, K., Hirokane, G., Morita, S., Yokono, A., Inoue, Y. and Takahashi, S.: "The effect of cytochrome P4502D6 genotypes on haloperidol metabolism : A preliminary study in a psychiatric population."Psychiatry Clin Neurosci. 53(5). 593-597 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Someya, T., Muratake, T., Hirokane, G., Shibasaki, M., Shimoda, K. and Takahashi, S.: "Interindividual variation in bromperidol metabolism and its relationship with therapeutic effects."J Clin Psychopharmacol. (in press).
Description
「研究成果報告書概要(欧文)」より
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