2012 Fiscal Year Final Research Report
Searching of early predictive marker in sorafenib-induced hepatotoxicity
| Project/Area Number |
23790169
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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
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| Research Institution | Tohoku University |
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Principal Investigator |
SUZUKI Hiroyuki 東北大学, 大学院・医学系研究科, 助教 (50588978)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 薬物動態・代謝学 / 抗がん剤 |
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| Research Abstract |
The purpose of this study was to explore the predictive marker for liver injury caused by sorafenib-treatment. From the results using hepatoma cells, it showed that sorafenib itself was due to occurring liver injury. In addition, sorafenib N-oxide also showed cytotoxicity, which N-oxide might convert to sorafenib in cells. Sorafenib is metabolized to sorafenib N-oxide via CYP3A4 in human liver. Combined together, when CYP3A4 function decreased in a patient, sorafenib convert ration maintained high level in serum. Therefore, this pharmacokinetic profile may be a key role for causing liver injury.
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