National Institute of General Medical Sciences. One

The metabolism of ‘4C-triamterene (TA). 2.4.7-triamino-6-phenylpteridine. was investigated in rats. After administration of ‘4C-TA (2 mg/kg. sc). 45 % and 50 % of the total radioactivity was excreted in urine and feces. respectively. during 72 hr. ‘4C-TA and its metabolites were separated by paper chromatography and countercurrent distribution. Unchanged TA in the urine and feces accounted for 72-79 % of the dose. The major metabolites in the excreted dose were free p-hydroxytriamterene (1 0- 1 5%) and its conjugate ( 1-5%). Three hours after administration of the drug. the major metabolites were not found in gastrointestinal contents or urine when the bile duct was cannulated. They were formed in the liver and secreted in bile. A minor unidentified metabolite (2 % of the dose) was also formed in the liver and excreted in urine and feces. Triamterene (TA) ’ is a diuretic agent which possesses an effective potassium-sparing effect. Although a nucleotide of TA was isolated from kidneys of rats which received TA ( 1), its metabo-lism in the rat has not been studied. In addition to unchanged TA, three metabolites, which were identified as triameterene N-glucuronide, p-hydroxytriamterene, and its sulfate, were excreted in the urine ofhumans who ingested TA (2, 3). It is not known whether the metabolism of TA in the rat is similar to that in the human. The contribu-tion of biliary and fecal excretions of TA and it