THE DISTRIBUTION, EXCRETION, AND METABOLISM OF METHYLGLYOXAL-bis-GUANYLHYDRAZONE-C¹⁴

¹ Clinical Pharmacology and Experimental Therapeutics Service, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

The fate of radioactive methylglyoxal-bis-guanylhydrazone (methyl-GAG-C¹⁴) has been studied in the mouse, rat, dog, and monkey following single parenteral and oral doses.

One-half and 2 hours after parenteral administration in mice, radioactivity was present in all tissues and organs examined but was predominant in the liver, small and large intestines with contents, kidneys, and urine. Expired CO₂ collected for 24 hours contained no radioactivity.

Following parenteral dosage at several levels, two-thirds of the radioactivity was recovered in the urine and less than one-fifth in the feces after 48 hours. The liver contained less than 0.5% of the radioactivity by this time. In contrast, three-fourths of the radioactive dose was recovered in the feces 24 hours following oral administration.

In rats, similar results were obtained on the excretion of radioactivity except after 48 hours, rat liver contained more radioactivity than mouse liver. A significant amount of radioactivity was not excreted in rat bile. In both rodent species, more than 48 hours were required for approximately complete recovery of the radioactive dose in the urine and feces.

Following parenteral administration of a single dose of methyl-GAG-C¹⁴ in dogs, the urinary excretion of radioactivity is much more protracted than in rodents with only one-half of the dose recoverable in 72 hours. This protraction in urinary excretion of radioactivity was not as pronounced in the monkey which excreted less than one-half of the radioactive dose in 24 hours following parenteral administration.

Urine samples were analyzed by paper chromatography, high-voltage paper electrophoresis and ion-exchange column chromatography on Bio-Rex 70 to characterize the molecular species of the C¹⁴. In all cases, the excreted radioactivity was identified as methyl-GAG. Thus, methyl-GAG was excreted unaltered in the animals studied.

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