2001 Fiscal Year Final Research Report Summary
Grapefruit juice-drug interaction and the prediction
| Project/Area Number |
12557225
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tohoku University |
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Principal Investigator |
YAMAZOE Yasushi Tohoku Univ., Grad. Sch. of Pharm. Sci., Prof., 大学院・薬学研究科, 教授 (00112699)
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| Co-Investigator(Kenkyū-buntansha) |
OHASHI Kyoichi Hamamatsu Med. Univ., Prof., 教授 (20137714)
FUKUDA Katsuyuki Tanabe Pharm. Co., Res., 研究院
NAGATA Kiyoshi Tohoku Univ., Grad. Sch. of Pharm. Sci., Ass. Prof., 大学院・薬学研究科, 助教授 (80189133)
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| Project Period (FY) |
2000 – 2001
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| Keywords | grapefruit juice / drug interaction / drug metabolism / enzyme inhibition |
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| Research Abstract |
Grapefruit-drug interaction was investigated to understand the mechanism and influence on drug therapy. We first identified the causative chemicals in grapefruit juice as furanocoumarin-geranylderivatives including GF-I-1 and GF-I-4. These chemicals were found to be strong inhibitors of a human cytochrome P450, CYP3A4. We showed that less than 50 ml intake of the juice altered the kinetic profile of midazolam, which was metabolized by CYP3A4. Selective influence of the juice on intestinal CYP3A4 was shown with volunteers taking omeprazole. Furanocoumarins were shown to decrease intestinal CYP3A4 by both competitive and inactivation, possibly through intermediate complex formation. In addition, we found that grapefruit intake suppress DNA lesion induced by dietary carcinogen PhIP. We are currently investigating the chemoprevention mechanism. To assess the influence of the juice component on CYP3A4 induction, we are developing the in vitro assay system of CYP3A4 gene activation. We have a plan to test the furanocoumarins for the inducibility of CYP3A4.
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