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Excretion of probenecid and its metabolites in bile and urine of rats.

The metabolites of probenecid excreted in the bile of rats with and without ligation of the renal pedicles were investigated using a new GLC assay procedure. Within 8 hr after administration, 63.8% of a 40-mg/kg iv dose of probenecid was accounted for in the bile of normal, anesthetized rats. The metabolites found (as percent of dose) include probenecid (10.0%), probenecid glucuronide (15.7%), glucuronide of the N2-hydroxypropyl derivative (20.3%), glucuronide of the N-3-hydroxypropyl derivative (14.2%), and the unconjugated N-2-carboxyethyl derivative (3.6%). Ligation of the renal pedicles increased the excretion of each metabolite, raising the total recovery to 86.6%. These oxidized metabolites, but not probenecid or its glucuronide, were excreted in urine in unconjugated form (3–5% each). The unconjugated mono-N-depropylated metabolite accounted for 11.2% of the dose in the urine of normal, unanesthetized rats but was not found in the bile of the anesthetized animals.