フロセミド及びその代謝物の高速液体クロマトグラフィーによる血漿及び尿中濃度測定と臨床応用

概要

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A method of high performance liquid chromatography for the determination of unchanged furosemide and its metabolites in the plasma and urine of human subjects is reported. A reversed phase Hibar Lichrosorb RP-8 column was applied to the present method. Furosemide from samples was extracted with diethylether. Beta-glucronidate of furosemide was determined after the addition of beta-glucronidase. 4-Chloro-5-sulfamoyl-anthranilic acid (CSA) was determined by the supernatant obtained from ten minutes centrifugation of the urine with ethanol. In the plasma and urine concentrations of unchanged furosemide of healthy volunteers, there were recognized differences among individuals. In patients with chronic renal failure, urine concentration of beta-glucronidate of furosemide increased in response to impairment of creatinine clearance. CSA could be detected only in the urine of patients receiving renal transplantation under a large dose administration of furosemide (above 200mg/d during rejection). And CSA does not seem to be an artifact product by the procedures of extraction. No interference could be observed by the drugs co-administered with furosemide. The present method can be utilized for a routine drug monitoring system of furosemide. Mechanism of formation of metabolites of furosemide should be further studied.
社団法人日本薬学会の論文
1988-11-25