Analysis of drug absorption behavior under gastrointestintestinal diseases related with abnormal metabolism of serotonin
| Project/Area Number |
26460197
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Okayama University |
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Principal Investigator |
Higaki Kazutaka 岡山大学, 医歯薬学総合研究科, 教授 (60284080)
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| Co-Investigator(Kenkyū-buntansha) |
大河原 賢一 岡山大学, 医歯薬学総合研究科, 准教授 (30291470)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 腸神経系 / セロトニン枯渇 / 経口吸収挙動 / 有機アニオン系化合物 / 消化管内移行速度 / bioavailability / 非線形性 / GITA model / 分泌 / 小腸内滞留性 / 胃排出 / 腸移行速度 / 平均滞留時間 / MRP2 / BCRP |
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| Outline of Final Research Achievements |
It is known that 5-HT regulating the gastrointestinal (GI) motility and function is deeply related with several serious GI diseases such as irritable bowel syndrome. In this study, we examined the effect of 5-HT depletion on oral absorption of an organic anion drug by utilizing phenol red (PR) as a model drug. 5-HT depletion significantly decreased PR absorption at low dose of PR, but tended to increase it at its high dose. The enhancement of luminal secretion by Mrp2 and BCRP induced by 5-HT depletion and it functional saturation, and the change in permeability via passive diffusion would be responsible for the dose-dependent difference for the effect of 5-HT depletion on PR absorption. Furthermore, 5-HT depletion accelerated GI-transit at upper segments, but suppressed it at lower segments, suggesting that the sequential propagation of GI- motility from proximal to distal segments was disordered.
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Report
(4 results)
Research Products
(2 results)
