Absorption and Distribution Characteristics of 5-Fluorouracil (5-FU) after an Application to the Liver Surface in Rats in Order to Reduce Systemic Side Effects
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概要
- 論文の詳細を見る
The present study was undertaken to elucidate the absorption and distribution characteristics of 5-fluorouracil (5-FU) after its application to the liver surface in rats to examine the possibility of reducing the systemic side effects of this agent. 5-FU was applied to the surface of the liver by employing a cylindrical diffusion cell. Approximately 69% of the dose was absorbed in 360 min. The time course of the change in the amount of 5-FU remaining in the diffusion cell obeyed first-order kinetics. Also, a linear relationship was observed between the apparent permeability coefficient, Papp, and the reciprocal of the square root of the molecular weight of several compounds including 5-FU. The estimated Papp value of 5-FU was in good agreement with the experimental value. The plasma concentration of 5-FU was low (<1.2 μg/ml) until 360 min after the application. Following i.v. administration, 5-FU was rapidly eliminated from the plasma and could not be detected at 120 min. In the analysis of tissue distribution, the liver was divided into three sites; the region under the diffusion cell attachment site (site 1), the treated lobe excluding site 1 (site 2), and untreated lobes (site 3). After being administered i.v., 5-FU mainly distributed in the kidney, and the concentration in the liver was significantly lower than that in kidney, spleen, or heart. After its application to the liver surface, however, 5-FU preferentially distributed at site 1, and was not detected at the other sites or in other tissues. Thus, these results suggested the possibility of a reduction in the systemic side effect of 5-FU on its application to the liver surface.
- 社団法人日本薬学会の論文
- 2008-05-01
著者
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中島 幹夫
佐賀大学医学部附属病院 手術部
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中島 幹夫
佐賀医科大学手術部
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中村 純三
Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.
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NISHIDA Koyo
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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FUMOTO Shintaro
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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NAKAMURA Junzo
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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NAKASHIMA Mikiro
Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry
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SASAKI Hitoshi
Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry
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Nakamura J
Faculty Of Pharmaceutical Sciences Nagasaki University
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Nakamura Junzo
長崎大学 薬
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Nakamura Junzo
School Of Pharmaceutical Sciences Nagasaki University
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Nishida K
Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.
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Nakashima M
Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.
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Nakashima M
Department Of Hospital Pharmacy Nagasaki University Hospital Of Medicine And Dentistry
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Nakashima Mikiro
Department Of Hospital Pharmacy Nagasaki University School Of Medicine
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Fumoto Shintaro
京都大学 薬学研究科薬品動態制御学
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Sasaki H
Dep. Of Hospital Pharmacy Nagasaki Univ. Hospital
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NISHI JUNYA
Graduate School of Biomedical Sciences, Nagasaki University
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KODAMA Yukinobu
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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NISHI Junya
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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Kodama Yukinobu
Graduate School Of Biomedical Sciences Nagasaki Univ.
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Nakano M
Department Of Laboratory Medicine Nagasaki University School Of Medicine
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Sasaki Hitoshi
長崎大学 医歯学部病院薬剤部
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Sasaki Hitoshi
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Shiota H
Nagasaki Univ. Nagasaki Jpn
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Sasaki Hajime
Semiconductor Group Mitsubishi Electric Corporation
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Sasaki Hideyuki
R&d Center Toshiba Corp.
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Sasaki H
Central Research Laboratories Zeria Pharmaceutical Co. Ltd.
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Sasaki H
Electrotechnical Laboratory
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Sasaki H
Nagasaki Univ. School Of Medicine Nagasaki Jpn
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Sasaki Hitoshi
Department Of Hospital Pharmacy Nagasaki University Hospital
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Fumoto Shintaro
Graduate School Of Biomedical Sciences Nagasaki Univ.
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Nakashima Mikiro
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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