Kinetic Study on the Mechanism of Tissue Distribution of Vinblastine
スポンサーリンク
概要
- 論文の詳細を見る
The purpose of present study was to analyze the factors involved in the tissue distribution of vinblastine (VBL). The specific binding of VBL to mouse tissue cytosol determined by a charcoal method correlated well with the tissue concentration of tubulin, a target protein for the pharmacological activity of Vinca alkaloids. The calculated tissue-to-plasma partition coefficients (K_p) in various tissues, based on the VBL binding to 100000×g cytosols showed a good correlation with the corresponding in vivo K_p values of rats reported in the literature, however, the calculated K_p values were greatly underestimated. The total binding (including specific and non-specific bindings) to cytosols from the liver and kidney, determined with the ultrafiltration method, were approximately 5 times higher than those determined with the charcoal method for both tissues. However, the total bindings to cytosol cannot explain the high K_p values in vivo. Considering the intracellular distribution of VBL, it was found that cytosol is not the main binding component for VBL since approximately one-half of the VBL in the liver homogenate was associated with the nuclear fraction. The K_p value in the liver, calculated by considering the intracellular distribution, became close to the in vivo K_p value. It was concluded that the tissue distribution of VBL connot be accounted for only by the binding to tubulin. and that the bindings to other intracellular components should also be included.
- 公益社団法人日本薬学会の論文
著者
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Sugiyama Yuichi
Grad. Sch. Pharm. Sci. Univ. Tokyo
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Wierzba Konstanty
東京都医学研究機構東京都臨床医学総合研究所
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Wierzba Konstanty
東京大学 薬
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Wierzba Konstanty
Faculty Of Pharmaceutical Sciences University Of Tokyo
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Wierzba Konstanty
Taiho Pharmaceutical Co. Ltd. Hanno Research Center
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HANANO Manabu
Faculty of Pharmaceutical Sciences, University of Tokyo
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SUGIYAMA Yuichi
Faculty of Pharmaceutical Sciences, University of Tokyo
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IGA Tatsuji
Faculty of Pharmaceutical Sciences, University of Tokyo
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IGA Tatsuji
International University of Health and Welfare
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Hanano Manabu
Faculty Of Pharmaceutical Sciences University Of Tokyo
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Hanano M
Department Of Pharmaceutics College Of Pharmacy Nihon University
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Hanano M
Department Of Pharmaceutical Science College Of Pharmacy Nihon University
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Hanano Manabu
Faculty Of Pharmaceutical Science University Of Tokyo
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Sugiyama Yuichi
Faculty Of Pharmaceutical Sciences University Of Tokyo
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Iga T
Department Of Pharmacy University Of Tokyo Hospital
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Iga Tatsuji
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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Iga Tatsuji
Faculty Of Pharmaceutical Sciences University Of Tokyo
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Hanano M
Faculty Of Pharmaceutical Sciences University Of Tokyo
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Hanano Manabu
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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Iga T
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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Iga Tatsuji
Department Of Pharmacy Faculty Of Pharmaceutical Sciences University Of Tokyo
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Sugiyama Yuichi
Faculty Of Pharmaceutical Sciences The University Of Tokyo
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Iga Tatsuji
Division Of Gastroenterology Department Of Medicine Kurume University School Of Medicine
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IGA TATSUJI
Department of Pharmaceutics, University of Tokyo Hospital, University of Tokyo
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