Establishment of pharmacogenetic-based dosing algorithm of warfarin for Asian, Caucasian and African American patients
| 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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Report
(4 results)
Research Products
(38 results)
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[Journal Article] Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study2013
Author(s)
Perera MA, Cavallari LH, Limdi NA, Gamazon ER, Konkashbaev A, Daneshjou R, Pluzhnikov A, Crawford DC, Wang J, Liu N, Tatonetti N, Bourgeois S, Takahashi H, et al.
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Journal Title
Lancet
Volume: 382
Issue: 9894
Pages: 790-796
DOI
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Peer Reviewed
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[Presentation] The determinant factors to influence on the warfarin adjustment period2011
Author(s)
Okazaki H, Inami S, Horibe A, Nakajima M, Takao A, Watanabe A, Takagi G, Takano H, Miyauchi Y, Asai K, Yasutake M, Takahashi H, Shimada T and Mizuno K
Organizer
第75回日本循環器学会総会・学術集会
Place of Presentation
横浜
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