アスピリン尿中代謝物による薬物代謝酵素活性測定法の試み

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The effect of the inducers of drug-metabolizing enzymes on the urinary excretion of aspirin metabolites in rats was studied. As to the inducer, rats were administered polychlorinated biphenyls (KC-500:10, 50, and 100 mg/kg b.w.), phenobarbital (80 mg/kg b.w.), or 3-methylcholanthrene (25 mg/kg) intraperitoneally once a day for three days. The rats were orally administered aspirin (50 mg/kg) on the second-10 th day after the pre-treatment with each inducer, and the urine were collected respectively. Aspirin metabolites (salicylic acid, salicyluric acid, and gentisic acid) in the urine were simultaneously determinated with high-performance liquid chromatography and the liver microsomal cytochrome P-450 was determinated. The results obtained were as follows. 1) Excretion rate of total gentisic acid and salicylate glucuronide in the urine collected for first 6 hours were increased significantly by the pre-treatment with KC-500 or phenobarbital. 2) In the pre-treated rats with various dose of KC-500, positive correlation was observed between the amount of liver microsomal cytochrome P-450 and the urinary excretion rate of gentisic acid (p<0.001). 3) Salicylic acid hydroxylating activity of liver microsome was increased in the rats pre-treated with KC-500, phenobarbital, or 3-methylcholanthrene. These results show that the increased urinary excretion of total gentisic acid and salicylate glucuronide may be due to the induction of drug-metabolizing enzymes in the liver. Therefore, it may be expected that these two aspirin metabolites are good indicators for the estimation of the activities of drug-metabolizing enzymes in vivo.
社団法人日本産業衛生学会の論文
1983-09-20

アスピリン尿中代謝物による薬物代謝酵素活性測定法の試み

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