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Individual therapy due to CYP genetic polymorphisms in patient with epilepsy

Research Project

Project/Area Number 17590123
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionOkayama University

Principal Investigator

GOMITA Yutaka  University Hospital, Professor, 医学部・歯学部附属病院, 教授 (00088709)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Kenji  Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (10037286)
SENDO Toshiaki  University Hospital, Associate Professor, 医学部・歯学部附属病院, 助教授 (30437561)
KITAMURA Yoshihisa  Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (40423339)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsDrug metabolism / CYP2C / CYP3A / Carbamazepin / gene polymorphism / mRNA / Real-time PCR / Individual therapy / フェニトイン / PCR
Research Abstract

The purpose of this project is to avoid the side effects due to drug interaction by characterizing the individual gene polymorphisms in patients with epilepsy. First, we developed the real-time PCR analysis for CYP3A13 and CYP2C11 in blood or liver in rat. To verify the usefulness as biomarker for metabolic ability, mRNA expression and protein content of CYPs was assayed at 3, 6, 12, 24 hr after final administration of carbamazepin ( 50 mg/kg, concecutive 2 weeks) in rat. The mRNA expression and protein content of CYPs showed different time profile. The CYP2C11 mRNA in blood was not detectable, thereof was not useful biomarker. The liver and blood content of CYPmRNA at 3 hr after carbamazepin administration showed a significant correlation. Therefore, it was expected that suitable sampling time was 3 hr after administration. The metabolic ability was estimated by the ratio of AUC (0-3 hr) of carbamazepin-epoxide, main metabolite to carbamazepin. It was clarified that the correlation between metabolic ability and mRNA expression or protein content of CYP3A13 was influenced by the dose. The findings obtained in this project provide a useful information to recommend the dosage planning every individual patient.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (2 results)

All 2006

All Journal Article (2 results)

  • [Journal Article] カルバマゼピン投与ラットにおける血中と肝臓中の産生CYPmRNAの相関性の検討2006

    • Author(s)
      林 瑶子
    • Journal Title

      TDM研究 23(3)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Correlation between Liver and Blood Content of CYPmRNA after Administration of Carbamazepin in Rats2006

    • Author(s)
      Hayashi, Yoko
    • Journal Title

      The Japanese Journal of Therapeutic Drug Monitoring 23 (3)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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