The antineoplasmic agent, cyclocytidine (2, 2'-anhydro-i-β-D-arabinofurano-sylcytosine hydrochloride), was examined for distribution, excretion and metabolism in rhesus monkeys. These monkeys have a high activity of cytidine deaminase in their tissues, as well as human beings. When monkeys were injected intravenously with
3H-cyclocytidine, high concentrations of radioactivity were detectable in the kidney, liver, pancreas and adrenal gland. The cumulative content of
3H in the urine reached approximately 37% of the administered dose for 320 min after the injection. A very small amount of
3H was found in the lumen of the digestive tract. It was suggested that the urinary passage might be a predominant route for the excretion of cyclocytidine. When monkeys received an oral dose of the labeled compound, the concentration of
3H was the highest in the kidney and liver of all the organs tested, as seen in the case of intravenous injection. Orally administered
3H-cyclocytidine underwent a metabolic destruction to
3H-arauridine (1-β-D-arabinofuranosyluracil) through
3H-aracytidine (1-β-D-arabinofuranosylcytosine) and finally to
3H-water in the digestive tract. When monkeys were sacrificed 2, 880 min after oral administration with
3H-cyclocytidine, there was an increase in the relative value of this labeled compound to
3H-aracytidine,
3H-arauridine, and
3H-water accompanied by the transport of the intestinal contents containing the
3H-compounds to the anal portion. The cumulative content of urinary
3H and the residual amount of
3H in the digestive tract were approximately 72 and 15% of the administered dose, respectively, for the same period of exposure. This sufficient recovery of radioactivity may reflect the production of
3H-water from the labeled compound by decomposition.
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