Studies on the Urinary Metabolites of Isophosphamide and Its Activated Species in Rabbits
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概要
- 論文の詳細を見る
Investigations on the urinary metabolites of isophosphamide, 4-hydroxyisophosphamide and 4-hydroxyisophosphamide including stereoisomers of the C_4-oxidized derivatives in rabbits revealed that their metabolic behaviors were different from each other and also form those of cyclophosphamide. Administration of isophosphamide to rabbits resulted in the urinary excretion of carboxyisophosphamide and two N-dechloroethylated metabolites besides considerable amount of unchanged isophosphamide, while 4-hydroxyisophosphamide was metabolized principally into carboxyisophosphamide. In the case of 4-hydroxyisophosphamide, carboxyisophosphamide was excreted as a major metabolite, but considerable amount of a new metabolite which might be produced from 4-ketoisophosphamide via a hitherto unknown pathway was also excreted besides small amount of 4-ketoisophosphamide. Mechanism of the formation of this new metabolite was proposed based on the chemical conversion of a suggested intermediate into the metabolite. PHosphorus configuration of the C_4-oxidized isophosphamides was found to have no significant effect upon their metabolism. It was suggested that the results of the present studies could account for the great differences in in vivo antitumor activities between isophosphamide and its pre-activated derivatives and also between isophosphamide and cyclophosphamide.
- 公益社団法人日本薬学会の論文
- 1977-11-25
著者
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高見沢 映
Shionogi Research Laboratory, Shionogi & Co., Ltd.
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岩田 豪
Shionogi Research Laboratory, Shionogi & Co., Ltd.
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高見沢 映
新潟薬科大学
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岩田 豪
Shionogi Research Laboratory Shionogi And Co. Ltd.
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高見沢 映
Shionogi Research Laboratory Shionogi & Co. Ltd.
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松本 佐市
Shionogi Research Laboratory, Shionogi and Co., Ltd.
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松本 佐市
Shionogi Research Laboratory Shionogi And Co. Ltd.
関連論文
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- Studies on Pyrimidine Derivatives and Related Compounds. XLVI. The Reactions of Diethyl Acetylphosphonate with Thiamine : Takamizawa Reaction (5).
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- チアミン遊離塩基と臭化シアンあるいは過酸化水素との反応
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