DISPOSITION OF 5-(3,3-DIMETHYL-1-TRIAZENO)IMIDAZOLE-4-CARBOXAMIDE, A NEW ANTITUMOR AGENT

¹ Department of Developmental Therapeutics, The University of Texas at Houston, M. D. Anderson Hospital and Tumor Institute, and Graduate School of Biomedical Sciences, Houston, Texas

In the mouse, after an i.p. injection of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide-2-¹⁴C (DIC-2-¹⁴C),50 mg/kg,55.8% of the injected radioactivity was in the carcass at 15 minutes, diminishing to 4.7% at 24 hours. The small intestine with content and the liver were the next highest in radioactivity. Other organs contributed insignificantly to the distribution. Similar studies with DIC-dimethyl-¹⁴C gave comparable results except that 9.3% of the injected dose appeared in the expired air as ¹⁴CO₂. Also 13.8% of the dose was in the urine at 15 minutes and 43.5% at 24 hours; in contrast, with DIC-2-¹⁴C, the corresponding percentages were 5.9 and 91.7%, respectively. Organ distribution of radioactivity in tumor-bearing mice was not markedly different from that in normal animals except that less ¹⁴CO₂ was expired. The cumulative urinary excretion of radioactivity in the dog after an i.v. injection of 20 mg/kg of DIC-2-¹⁴C was 40 to 66% in five hours, 36 to 84% of this representing unchanged DIC. In humans, the dog and the mouse, the major metabolite of DIC was 5-aminoimidazole-4-carboxamide. Part of the 5-aminoimidazole-4-carboxamide was excreted in the urine, and the rest entered the normal metabolic pathway.

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