Metabolites of 5-3H-Cyclocytidine in Monkeys Given Single Intravenous Injection

Abstract

Newly synthesized 5-3H-cyclocytidine was injected intravenously in rhesus monkeys having a high level of cytidine deaminase which inactivates aracytidine, an antitumor substance analogous to cyclocytidine, in human plasma and tissues. After rapid distribution as intact molecule in the liver, kidney, spleen, and other organs, 46.5% of the administered radioactivity was excreted via the renal pathway within 160 min. Metabolite analysis of 5-3H-cyclocytidine in plasma, tissues, and urine of the monkeys revealed that extensive or rapid degradation of cyclocytidine did not occur, and confirmed the resistance of cyclocytidine against the deaminase activity and its stability in biological condition in vivo. Phosphorylated derivatives of cyclocytidine were also detected in the monkey liver after injection. © 1975, The Pharmaceutical Society of Japan. All rights reserved.