Change in the PK profile of metabolites by inhibition of metabolic enzyme: elucidation of mechanism and establishment of predictive method
| Project/Area Number |
25870941
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
Drug development chemistry
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| Research Institution | Setsunan University |
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Principal Investigator |
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| Research Collaborator |
HASEGAWA Tsubasa 摂南大学大学院, 薬学研究科
NAKANISHI Satomi 摂南大学, 薬学部
HATAYAMA Syo 摂南大学, 薬学部
ONO Yasuaki 摂南大学, 薬学部
UEDA Akihiro 摂南大学, 薬学部
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 薬物相互作用 / CYP3A4 / 代謝物 / CYP阻害 / CYP3A / 薬物間相互作用 / 代謝物毒性 |
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| Outline of Final Research Achievements |
In order to predict the change in the PK profile of metabolites in DDI induced humans, PK profiles of parent drugs and metabolites in rats and monkeys were investigated. It was found that the systemic exposure of not only parent drugs but also their metabolites was significantly increased by DDI. Furthermore, this phenomenon was also observed in monkeys in which systemic clearance is comparable to that in humans. These findings indicated that significant increase of systemic exposure of metabolites by DDI could observe in humans. Metabolic activity and the change in it by DDI in the part of metabolic organ are important to determine the PK profile of metabolites. The mathematical modeling has been made to simulate our finding phenomenon, which can be useful to understand and predict the change in the PK profile of metabolites by DDI.
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Report
(3 results)
Research Products
(6 results)
