| Project/Area Number |
17590123
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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 |
Medical pharmacy
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| Research Institution | Okayama University |
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Principal Investigator |
GOMITA Yutaka University Hospital, Professor, 医学部・歯学部附属病院, 教授 (00088709)
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| 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)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| 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)
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| Keywords | Drug metabolism / CYP2C / CYP3A / Carbamazepin / gene polymorphism / mRNA / Real-time PCR / Individual therapy / フェニトイン / PCR |
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| 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.
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