KY-109,New Bifunctional Prodrug of Cephalosporin. II. : Mechanism of Oral Absorption
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概要
- 論文の詳細を見る
(5-Methyl-2-oxo-1,3-doxol-4-yl)methyl (6R, 7R)-7-[(R)-2-[(S)-alanyloxy]-2-phenylacet-amido]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate hydrochloride (KY-109) is a bifunctional prodrug designed to improve the oral absorption of the parent drug (KY-087), which is a cephalosporin with a broad spectrum of antibacterial activity.The mechanism of oral absorption of KY-109 was investigated in rats. An aqueous solution of KY-087 and a suspension of KY-106,which is esterified with a (5-methyl-2-oxo-1,3-dioxol)methyl group at the C-4 carboxy group of KY-087,were poorly absorbed orally in rats. However, a 50% propylene glycol solution of KY-106 and an aqueous solution of KY-109 were well absorbed. KY-109 was rapidly hydrolyzed to KY-106 in the small intestinal contents, though it was hardly hydrolyzed in the stomach contents. FUrther, KY-109 was hydrolyzed to KY-087 via KY-106 in the gastrointestinal homogenate.From these results, the mechanism of the oral absorption of KY-109 can be speculated to be as follows. KY-109 is transferred into the small intestinal lumen without hydrolysis in the stomach, and is then hydrolyzed to KY-106 with the release of the alanyl residue. The resulting KY-106 is then transferred into the mucosal membrane, and hydrolyzed enzymatically with the formation of KY-087 along with acetoin. The resulting KY-087 is then transferred into the blood stream.
- 公益社団法人日本薬学会の論文
- 1988-06-25
著者
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掛谷 宣治
Research Laboratories Kyoto Pharmaceutical Industries Ltd.
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西村 憲一
京都薬品工業株式会社
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中村 正平
Research Laboratories Kyoto Pharmaceutical Industries Ltd.
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中村 正平
京都薬品・研究部
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吉見 彰久
Research Laboratories Kyoto Pharmaceutical Industries Ltd.
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西沢 進
Research Laboratories Kyoto Pharmaceutical Co. Ltd.
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西村 憲一
Research Laboratories, Kyoto Pharmaceutical Co., Ltd.,
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西村 美年子
Research Laboratories, Kyoto Pharmaceutical Co., Ltd.,
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西村 美年子
Research Laboratories Kyoto Pharmaceutical Co. Ltd.
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