Determination of Paeonol Metabolites in Man by the Use of Stable Isotopes

概要

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The metabolism of paeonol (2-hydroxy-4-methoxyacetophenone : I) in man was studied by a stable isotope tracer technique. For the qualitative analysis of metabolites, an aliquot of 24 h urine from a man who had recived orally an equimolar mixture of I and I [methoxy-d_3,acetyl-^<13>C_2] was investigated by mass chromatography. Paeonol, 2,5-dihydroxy-4-methoxyacetophenone (II) and resacetophenone (III) were identified as free, β-glucuronide, sulfate and enzyme-resistant conjugate form metabolites in the urine. In addition, by comparing the ion intensities of fragment ions of II and II-^<13>C_2d_3 and those of III and III-^<13>C_2,an isotope effect in the process of metabolism was found. This isotope effect was explained in terms of the metabolic switching phenomenon. By dilution analysis using I [methoxy-d_3], II [methoxy-d_3] and III [acetyl-^<13>C_2] as internal standards, the amounts of metabolites in the urine were determined. The excretion of this drug was very rapid ; the total amount of metabolites excreted in the urine within 24 h reached 78.8% of the dose (II 50.2%, III 21.0%, I 7.6%). Predominant metabolites were the β-glucuronide of II (28.8% of dose) and an enzyme-resistant conjugate form of II (23.9%).
公益社団法人日本薬学会の論文
1981-07-25