赤毛猿における ³H-cyclocytidine の分布および排泄

抄録

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.