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The development of tailor made treatment for depressive disorder with new antidepressants by pharmacogenomic analysis

Research Project

Project/Area Number 13671000
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionDokkyo University School of Medicine (2002)
Shiga University of Medical Science (2001)

Principal Investigator

SHIMODA Kazutaka  Dokkyo University School of Medicine, Department of Psychiatry, Associate Professor, 医学部, 助教授 (30196555)

Co-Investigator(Kenkyū-buntansha) OKAWA Masako  Shiga University of Medical Science, Department of Psychiatry, Professor, 医学部, 教授 (80160430)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsantidepressant / metabolism / interindividual difference / genetic polymorphism / cytochrome P450
Research Abstract

Nowadays, main therapeutic tools for mental disorders are pharmacotherapies. However, most of the psychiatrists prescribe the psychotropic drugs with no guideline or no theoretical background. In order to obtain "maximum clinical effect with minimum side effect" of the psychotropic drugs, we need to collect and utilize the information of the individual patients including the pharmacogenomic information and comprehensively analyze such information. In this research project, we tried to find the relationship between the activity of drug metabolizing enzyme such as cytochrome P450 or glucuronyl transferase (genotypes of drug metabolizing enzymes), genotypes of serotonin-noradrenaline transporter and the clinical effect of selective serotonin reuptake inhibitor and serotonin-noradrenaline reuptake inhibitor. In 2001, samples from 12 patients with affective disorders treated with paroxetine were analyzed. They were maintained at the same daily dose at least for two weeks to obtain steady state concentrations. Significant positive correlation between plasma concentrations of paroxetine and daily dose corrected for body weight was observed, however, no significant relationship between the genotype of cytochrome P450 and the plasma levels of paroxetine was found. In 2002, the samples from 44 patients treated with paroxetine were analyzed. The patients with 20, 30, 40mg/day of paroxetine showed 3.0, 6.66, 6.24 fold plasma concentrations compared to the drug concentrations in the patients with 10mg/day, respectively, which means non-linear pharmacokinetics of paroxetine. Again, no significant relationship between the genotype of cytochrome P450 2D6 and the plasma levels of paroxetine was found.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] T.Someya et al.: "Establishment of enzyme immuno-assay for measuring serum sultopride level"Therapeutic Drug Monitoring. 23. 277-281 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Suzuki et al.: "Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol"Therapeutic Drug Monitoring. 23. 363-368 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Yokono et al.: "The effect of CYP2C19 and CYP2D6 genotype on the metabolism of clomipramine in Japanese psychiatric patients"Journal of Clinical Psychopharmacology. 21. 549-555 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Shimoda et al.: "Lack of impact of CYP1A2 genetic polymorphism(C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position-2964 in the 5'-flanking region of CYP1A2)on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia"Progress in Neuro-Psychopharmacology and Biological Psychiatry. 26. 261-265 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Shimoda et al.: "The impact of CYP2C19 and CYP2D6 genotype on the metabolism of amitriptyline in Japanese Psyciatric patients"Journal of Clinical Psychopharmacology. 22. 371-378 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Suzuki et al.: "Effects of concomitant fluvoxamine on metabolism of alprazolam in Japanese psychiatric patients : Interaction with CYP2C19 mutated alleles"European Journal of Clinical Pharmacology. 58. 829-833 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Someya, K. Shimoda, T. Murataka, E. Nakajima, A. Shirai, H. Funaoka, T. Yashiki, H. Ishii, N. Sunahara and S. Takahashi: "Establishment of enzyme immuno-assay for measuring serum sultopride level"Therapeutic Drug Monitoring. 23. 277-281 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Suzuki, T. Someya, K. Shimoda, G. Hirokane, S. Morita, A. Yokono, Y. Inoue, S. Takahashi: "Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol"Therapeutic Drug Monitoring. 23. 363-368 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A. Yokono, T. Someya, S. Morita, G. Hirokane, M. Okawa and K. Shimoda: "The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramne in Japanese psychiatric patients"Journal of Clinical Psychophamacology. 21(6). 549-555 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Shimoda, T. Someya, S. Morita, G. Hirokane, A. Yokono, M. Okawa, S. Takahashi: "Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position - 2964 in the 5'-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia"Progress in Neuro-Psychopharmacology and Biological Psychiatry. 26. 261-265 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Shimoda, T. Someya, A. Yokono, S. Morita, G. Hirokane, S. Takahashi and M. Okawa: "The impact of CYP2C19 and CYP2D6 genotypes on the metabolism of amitriptyline in Japanese psychiatric patients"Journal of Clinical Psychopharmacology. 22. 371-378 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki, Y., Shinoiri, T., Muratake, T., Kawashima, Y., Shimoda, K. and Someya, T.: "Effects of concomitant fluvoxamine on metabolism of alprazolam in Japanese psychiatric patients: Interaction with CYP2C19 mutated alleles"Eur J Clin Pharmacol. 58. 829-833 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Someya, Y. Suzuki, S. Sato, Y. Kawashima, K. Shimoda, G. Hirokane, S. Morita, A. Yokono, Y. Inoue, S. Takahashi: "The effect of CYP2D6 genotypes on haloperidol metabolism in a Japanese psychiatric population"Neuropsychopharmaology (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Shimoda et al.: "Lack of impact of CYP1A2 genetic polymorphism(C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position-2964 in the 5'-flanking region of CYP1A2)on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia"Progress in Neuro-Psychopharmacology and Biological Psychiatry. 26. 261-265 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Shimoda et al.: "The impact of CYP2C19 and CYP2D6 genotypes on the metabolism of amitriptyline in Japanese psychiatric patients"Journal of Clinical Psychopharmacology. 22. 371-378 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Suzuki et al.: "Effects of concomitant fluvoxamine on metabolism of alprazolam in Japanese psychiatric patients : Interaction with CYP2C19 mutated alleles"European Journal of Clinical Pharmacology. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Someya et al.: "Establishment of enzyme immuno-assay for measuring serum sultopride level"Therapeutic Drug Monitoring. 23. 277-281 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Suzuki et al.: "Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol"Therapeutic Drug Monitoring. 23. 363-368 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.Yokono et al.: "The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramne in Japanese psychiatric patients"Journal of Clinical Psychopharmacology. 21. 549-555 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Shimoda et al.: "Lack of impact of CYP1A2 genetic polymorphism(C/A polymorphism at position 734 in intron I and G/A polymorphism at position-2964 in the 5'-flanking region of CYP1A2)on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia"Progress in Neuro-Psychopharmacology and Biological Psychiatry. 26. 261-265 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Shimoda et al.: "The impact of CYP2C19 and CYP2D6 genotypes on the metabolism of amitriptyline in Japanese psychiatric patients"Journal of Clinical Psychopharmacology. (印刷中).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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