| Project/Area Number |
23590173
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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 | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MIYAMOTO Ken-ichi 金沢大学, 附属病院, 教授 (30100514)
NISHIMURA Tomohiro 慶應義塾大学, 薬学部, 講師 (40453518)
SAWAMOTO Kazuki 金沢大学, 附属病院, 特任助教 (80608696)
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| Co-Investigator(Renkei-kenkyūsha) |
ASAKURA Hidesaku 金沢大学, 附属病院, 准教授 (60192936)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 薬物体内動態 / 医薬品副作用 / 科学療法 / トランスポーター / 薬物代謝酵素 / 薬物動態 / 化学療法 / 肥満 / 肝取り込み / ゲムシタビン / リネゾリド / タクロリムス / フェンタニル / バイオアベイラビリティー / 個の医療 / 体内動態変動 / 抗がん剤 / 経腸栄養 / 血中濃度モニタリング / 臨床試験 / 非線形 / チーム医療 |
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| Outline of Final Research Achievements |
We investigated hepatic uptake of gemcitabine (GEM) in rat and human. The uptake mechanism involved high- and low-affinity saturable components with Km values of micromolar and millimolar order, respectively. Our results suggested that the hepatic extraction of GEM is predominantly mediated by the low-affinity nucleoside transporter ENT2 at clinically relevant hepatic concentrations of GEM, the uptake would not be completely saturated. This is critical for hepatic arterial infusion (HAI), because saturation of hepatic uptake would result in a marked increase of GEM concentration, abrogating the advantage of HAI over i.v. administration in terms of severe adverse events. We investigated pharmacokinetics of linezorid (LZD) in rat and human. The incidence of thrombopenia was increased according to the increase of plasma concentration of LZD. We also found that long-term enteral nutrition affected that the expression of transporters and metabolic enzymes in the liver and small intestine.
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