Distribution and excretion of 3H-cyclocytidine in rhesus monkeys.

Abstract

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.