| Project/Area Number |
15590141
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Sciences |
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Principal Investigator |
MIZUMA Takashi Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Associate Professor, 薬学部, 助教授 (80229715)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Masahiro Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Professor, 薬学部, 教授 (20012669)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | intestinal availability / bioavailability / drug-drug interactions / drug-nutrient interactions / intestinal metabolism / sulfate conjugation metabolism / Caco-2 cells / 抱合代謝 / 腸管吸収 / カテキン / 相互作用 / 飲食物 / Caco-2 / 培養細胞 / 食物成分 / 薬物速度論 |
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| Research Abstract |
Our research group has studied on intestinal absorption of benzyl β-glucoside contained in Prunus mume according to the everted intestine and Ussing type chamber methods using rat small intestines. Both types of experiments showed that benzyl β-glucoside was absorbed and in part metabolized during absorption, and that β-glucoside was transported in part by Na^+/glucose cotransporter (SGLT1). Moreover, it was obtained a novel finding that the SGLT1-mediated transport increased the intestinal availability of benzyl β-glucoside. Glucuronidation and sulfation metabolism were studied in Caco-2 cells with α-naphthol, a model drug. Both metabolic activities could be detected in Caco-2 cell monolayers. Moreover, both metabolic activities were also found in Caco-2 cell suspensions. Sulfation metabolism of α-naphthol in cell monolayers was inhibited by isoproterenol or terbutaline (substrates for intestinal sulfotransferase), whereas transport of α-naphthol was increased. This shows that we could establish an in vitro system to detect both conjugative metabolism and absorption (transport) using Caco-2 cell monolayers and suspensions. Thereby, influences of dietary compounds on intestinal metabolism and absorption were assessed using this in vitro detection system. Sulfation metabolism of α-naphthol in cell suspensions was significantly inhibited by the presence of (-)-epigallocatechin gallate (EGCG), (±)-catechin and tannic acid. Glucuronidation metabolism was inhibited by the presence of (-)-EGCG. Sulfation and glucuronidation metabolism of α-naphthol were inhibited by the presence of (-)-EGCG, (±)-catechin and tannic acid. In contrast, the transport of α-naphthol across Caco-2 cell monolayers was enhanced. Thus, our study supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science showed drug-nutrients (dietary compounds) interactions in drug absorption raised by intestinal conjugative metabolism.
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