| Project/Area Number |
23590652
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Meiji Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SHIOMI Mari 明治薬科大学, 薬学部, 助手 (30300768)
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| Co-Investigator(Renkei-kenkyūsha) |
NANJHO Shuji 東邦大学, 医学部, 准教授 (70328615)
SASAKI Yasutuna 埼玉医科大学, 医学部, 教授 (20235279)
FUJITA Kenichi 埼玉医科大学, 医学部, 講師 (60281820)
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| Research Collaborator |
LEE T.M. Michael Institute of Biomedical Sciences, Academia Sinica
CAVALLARI Larisa H イリノイ大学シカゴ校, 薬学部, 准教授
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ワルファリン / 個体差 / 応答性 / CYP2C9 / VKORC1 / 遺伝子多型 / INR / CYP2C9*3 / CYP2C9*8 / VKORC1*2 / 人種差 |
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| Research Abstract |
To establish the initiating dosing algorithm of warfarin in 3 different populations (Asian, African American and Caucasians), pharmacokinetic (PK) and pharmacodynamic (PD) factors associated with inter-individual variability in anti-coagulation responses were investigated by performing the retrospective and prospective clinical studies.
Multivariate analyses showed that mutations of CYP2C9*8,CYP2C9*3,CYP2C9*2, sex and age were predictors of PK (clearance) and that mutations of VKORC1*2 & CYP4F2*3 and the baseline coagulation activity were predictors of PD (IC50 & the non-linear index). Furthermore, all results indicate that factors associated with the reduced metabolic activity of warfarin might be critical determinants of the over-anticoagulation response during initiation therapy in Asian patients.
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