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Regional delivery of model compounds and 5-Fluorouracil to the liver by their application to the liver surface in rats: its implication for clinical use


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タイトル: Regional delivery of model compounds and 5-Fluorouracil to the liver by their application to the liver surface in rats: its implication for clinical use
著者: Nishida, Koyo / Fujiwara, Rie / Kodama, Yukinobu / Fumoto, Shintaro / Mukai, Takahiro / Nakashima, Mikiro / Sasaki, Hitoshi / Nakamura, Junzo
発行日: 2005年 8月
出版者: Springer Netherlands
引用: Pharmaceutical Research, 22 (8), 1331-1337, 2005
抄録: PURPOSE: The purpose of this study was to examine drug distribution in the liver after drug application to the rat liver surface. METHODS: Phenolsulfonphthalein (PSP) and fluorescein isothiocyanate dextran (MW 4400, FD-4) as model compounds or 5-fluorouracil (5-FU) was applied to the rat liver surface by employing a cylindrical diffusion cell (i.d. 9 mm, 0.64 cm2). Then, blood and the remaining solution in the diffusion cell were collected at selected times, followed by excision of the liver. The excised liver was divided into three sites: the region under the diffusion cell attachment site (site 1), the applied lobe except for site 1 (site 2), and non-applied lobes (site 3). RESULTS: In the case of i.v. administration, there were no differences in PSP concentrations among the three sites of the rat liver, and the concentrations rapidly decreased. On the other hand, the PSP concentration in site 1 after application to the rat liver surface was considerably higher than in site 2 and site 3. In addition, the area under the curve (AUC) value (AUCsite1), calculated from the PSP concentration profile in site 1, was about 10 times larger than that in site 3. A similar trend of regional delivery advantage by liver surface application was observed in the case of the macromolecule model FD-4, with a marked AUCsite1 of about 5 times larger than the other two sites. Moreover, we clarified that the anticancer drug 5-FU preferentially distributed in site 1 after application to the rat liver surface. CONCLUSION: These results demonstrate the possibility of regional delivery of drugs to the liver by application to the liver surface.
URI: http://hdl.handle.net/10069/6486
ISSN: 07248741
DOI: 10.1007/s11095-005-5273-9
PubMed ID: 16078143
関連リンク : http://dx.doi.org/10.1007/s11095-005-5273-9
権利: The original publication is available at www.springerlink.com
資料タイプ: Journal Article
原稿種類: author
出現コレクション:050 学術雑誌論文

引用URI : http://hdl.handle.net/10069/6486

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