URINARY EXCRETION CHARACTERISTICS OF A POLYMERIC PRODRUG OF MITOMYCIN C, MITOMYCIN C-DEXTRAN CONJUGATE
スポンサーリンク
概要
- 論文の詳細を見る
Urinary excretion characteristics of a polymeric prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D), following intravenous administration was studied in rats. Three types of MMC-D, conjugates with dextrans of molecular weights of 10000,70000 and 500000,were tested and urine concentration of MMC, dextran and spacer were determined by three analytical methods, i.e., bioassay, anthrone method and radioactivity counting. MMC was assayed separately as a free form and conjugated form based on antimicrobiological activity. MMC administered as a free form was excreted rapidly into urine but only a small amount of MMC was excreted following the administration of MMC-D. The excreted amount of MMC in a conjugated form varied with the size of carrier dextran while similar sustained excretion was observed regardless of the carrier size. The excretion of carrier dextran determined by anthrone method was confined as the molecular weight was increased. The effect of molecular weight was also observed in the case of spacer-introduced dextran (dextran-C_6 spacer) and original dextran. Compared with neutral dextran, cationic MMC-D and anionic dextran-C_6 spacer exhibited diminished excretion, indicating the effect of charge on urinary excretion. The urinary recovery of radioactivity was almost in accordance with that of carrier dextran. However, the urinary recovery of MMC based on biological activity was considerably lower than that of carrier dextran. It was suggested that MMC-D underwent inactivation to a great extent before releasing active MMC in the body. The effect of physicochemical properties such as molecular weight and electric charge on the urinary excretion of the polymeric prodrug was thus elucidated.
- 公益社団法人日本薬学会の論文
著者
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Hashida Mitsuru
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Hashida Mitsuru
Faculty Of Pharmaceutical Sciences Kyoto University
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Hashida M
Departments Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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SEZAKI Hitoshi
Faculty of Pharmaceutical Sciences, Kyoto University
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Arimoto A
Hitachi Lab. Hitachi Ltd.
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Sasaki Hitoshi
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Sezaki Hitoshi
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Sezaki Hitoshi
Faculty Of Pharmaceutical Sciences Kyoto University
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Sezaki Hitoshi
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Hashida M
Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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Takakura Yoshinobu
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Takakura Yoshinobu
Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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HONDA Kazuo
Faculty of Medicine, Kyoto University
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SATOMURA KISAKU
the Second Department of Surgery, Faculty of Medicine, Kyoto University.
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Honda K
Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn
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Sasaki H
Nagasaki Univ. School Of Medicine Nagasaki Jpn
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Arimoto A
Hitachi Ltd. Tokyo Jpn
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Satomura Kisaku
The Second Department Of Surgery Faculty Of Medicine Kyoto University.
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