[Estimation of drug-metabolizing enzyme activities by measuring urinary metabolites of aspirin].

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-10th 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 determined with high-performance liquid chromatography and the liver microsomal cytochrome P-450 was determined. The results obtained were as follows. 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. 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 less than 0.001). Salicylic acid hydroxylating activity of liver microsome was increased in the rats pretreated 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.