PHARMACOKINETICS OF SPIRONOLACTONE AND POTASSIUM CANRENOATE IN HUMANS
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概要
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Plasma concentrations and urinary excretion of canrenone (III), canrenoic acid (IV) and canrenoic acid glucuronide (V) were determined by means of high performance liquid chromatography (HPLC) and fluorometry after oral administration of spironolactone (I) and potassium canrenoate (II) to human subjects. comparison of both assays for III in plasma as well as in urine after administration of I showed marked differences. Plasma concentrations of III were significantly higher after administration of II than I, C_<max> and AUC from II being 3-5 times larger than those from I by means of HPLC assay, while the fluorometrically determined values for III in plasma after administration of I and II did not differ as much from each other. On the other hand, in contrast to plasma, the amount of III excreted in urine after administration of I was much larger than that after II, i.e. 3-4 times greater by means of HPLC and over 10 times greater by means of fluorometry. These results strongly suggest that precursors of III are formed which have a higher renal clearance than that for III alone after oral administration of I. Considering the relative biological potency ratio of I and II, it is presumed that their pharmacological activities may relate to the urinary excretion of III. Plasma concentrations of IV were definitely higher after administration of II compared to those after I. Canrenoic acid (IV) was excreted mainly as glucuronide (V) in urine.
- 公益社団法人日本薬学会の論文
著者
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KOJIMA KENJI
Research and Development Division, Dainippon Pharmaceutical Co., Ltd.
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YAMAMOTO KAZUMITSU
Research and Development Division, Dainippon Pharmaceutical Co., Ltd.
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Fujioka Hiroshi
大日本製薬
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Yamamoto Kazumitsu
Research And Development Division Dainippon Pharmaceutical Co. Ltd.
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FUJIOKA HIROSHI
Research and Development Division, Dainippon Pharmaceutical Co. Ltd.
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KANEKO HIDEHIKO
Research and Development Division, Dainippon Pharmaceutical Co. Ltd.
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Kaneko Hidehiko
Department Of Electronic Engineering The National Defense Academy
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Kojima Kenji
Research And Development Division Dainippon Pharmaceutical Co. Ltd.
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Yamamoto Kazuo
Laboratory Of Molecular Medicine Department Of Integrated Biosciences Graduate School Of Frontier Sc
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YAMAMOTO KAZUMITSU
Research and Development Division, Dainippon Pharmaceutical Co. Ltd.
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