Studies on the Interaction of Pyridone Carboxylic Acids with Metals
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概要
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The stability constants of metal complexes for several pyridone carboxylic acid drugs (ofloxacin, norfloxacin and lomefloxacin) were determined by potentiometry and spectrophotometry. The values of aluminum complexes, magnesium complexes and calcium complexes were Ca<Mg≪Al. The stability constants of lomefloxacin complexed with divalent transition metal ions were determined and these values followed the Irving-Williams series (Mn<Fe<Co<Ni<Cu>Zn). The stability constants of metal complexes for several pyridone carboxylic acids synthesized were also determined and compared with those for pyridone carboxylic adic drugs. The stability constants of these compounds gradually increased with an increasing pK_a value of the carboxyl group of pyridone carboxylic acid. In the case of aluminum complexes, the complexes Al(OH)L and Al(OH)_2L were formed under weak acidic conditions and the dissociation constants for the hydrolysis of the aluminum complexes were determined. The participation of the carboxyl group and the carbonyl group in the chelating reaction was confirmed by the measurement of carbon-13 nuclear magnetic resonance of the aluminum complex and the magnesium complex. These results suggest that when pyridone carboxylic acids are administered with metallic antacid containing aluminum hydroxide and magnesium oxide, aluminum complexes AIL, Al(OH)L or Al(OH)_2L are formed and the adsorption of the drugs in the intestines is reduced.
- 社団法人日本薬学会の論文
- 1992-03-25
著者
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照井 彬弘
Shionogi Research Laboratories, Shionogi & Co., Ltd.
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北川 隆康
Shionogi Research Laboratories, Shionogi & Co., Ltd.,
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林 文晶
Shionogi Research Laboratories Shionogi & Co. Ltd.
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北川 隆康
Shionogi Research Laboratories Shionogi & Co. Ltd.
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岡林 義人
Shionogi Research Laboratories, Shionogi & Co., Ltd.
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岡林 義人
Shionogi Research Laboratories Shionogi & Co. Ltd.
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北川 隆康
塩野義製薬(株)研究所
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照井 彬弘
Shionogi Research Laboratories Shionogi & Co. Ltd.
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