| Project/Area Number |
24659073
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | Nagoya University (2013)
Kanazawa University (2012) |
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Principal Investigator |
YOKOI Tsuyoshi 名古屋大学, 医学(系)研究科(研究院), 教授 (70135226)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 医薬品副作用 / 薬物相互作用 / hypersensitivity / 皮膚障害 / 薬物性肝障害 / フェニトイン / カルバマゼピン / バイオマーカー / 薬物過敏症 / 薬物アレルギー / 免疫学的因子 / 反応性代謝物 / 代謝的活性化 |
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| Research Abstract |
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are major causes to attrition during clinical studies. Formation of reactive metabolites of drugs by drug-metabolizing enzymes has been focused. Considering the species differences and interindividual differences, studies for developing the prediction method of SJS/TEN in non-clinical drug development were conducted. However, SJS/TEN with very low incidence are hard to predict, because the immune- and inflammatory-related factors were not able be considered. Recently, we have established animal models of drug-induced liver injury in 10 kinds of clinical drugs. However, the phenotypic consequence of SJS/TEN in mouse model showed very low reproducibility, even with many difference experimental conditions. Thus, we clarified the mechanism of hepatic inflammation by carbamazepine and phenytoin (representative drugs for SJS/TEN) in mouse.
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