DISTRIBUTION AND EXCRETION OF CYCLOCYTIDINE IN MONKEYS, DOGS, AND RATS
1974 年 65 巻 2 号 p. 153-161
詳細
1974 年 65 巻 2 号 p. 153-161
The distribution in tissues and excretion of cyclocytidine (2, 2'-anhydro-1-β-D-arabinofuranosylcytosine hydrochloride) and its metabolites in urine and feces of macaca monkeys (Macaca irus, Macaca fuscata, and Macaca mulata) and in beagle dogs were examined by the spectrophotometric assay. Distribution of cyclocytidine in plasma and tissues of rats was also examined.
The administered cyclocytidine showed a half-life of 22min in plasma of dogs and monkeys, whereas the half-life of aracytidine (1-β-D-arabinofuranosylcytosine hydrochloride) was 47min in plasma of dogs and less than 5min in plasma of monkeys, because of rapid deamination of the comvound to arauridine (1-β-D-arabinofuranosyluracil) in the latter species. Cyclocytidine exhibited maximum concentration in tissues of rats and monkeys at 20 to 40min after the administration, but its metabolites, aracytidine and arauridine, were not detected in these tissues. Cyclocytidine levels in tissues diminished thereafter but were detected within the next 40 to 80min, Neither cyclocytidine nor its metabolites could be detected in the brain. When cyclocytidine was administered intravenously in dogs and monkeys, 65-85% of it was excreted in urine, almost all as intact cyclocytidine, and small amounts of aracytidine and arauridine were detected. On the other hand, the administered aracytidine was excreted only as arauridine in urine of monkeys, and aracytidine and arauridine in dogs. Cyclocytidine and its metabolites were not detected in feces of both species.
It might be suggested that the distribution and elimination rate of cyclocytidine after its intravenous administration is not affected by the presence of cytidine deaminase in plasma and tissues.
