Metabolic Fate of YNK01 (1): Absorption, Distribution, Metabolism and Excretion after Single Administration of [14C] YNK01 to Rats

Absorption, distribution, metabolism and excretion of [14C] 4-amino-1-β-D-arabinofuranosyl-2 (1H)-pyrimidinone 5'-(sodium octadecyl phosphate) monohydrate (YNK01) were studied in rats after single oral administration of 25mg/kg. 1. Blood concentration reached the highest concentration at 4 hours after dosing, and declined up to 12 hours with half life of 3.7 hours. 2. Radioactivity secreted to urine, feces and expired air amounted to 40.6, 43.8 and 15.6% of administered dose, respectively up to 120 hours after dosing. Radioactivity remaining in the body 120 hours after administration accounted for 1.4%. 3. Radioactivity in bile up to 48 hours after dosing amounted to 2.4% of the dose. 4. Radioactivity levels in tissues other than the eyes and the central nerve system were similar to or higher than that in blood. Radioactivity was distributed at particularly high levels in the small intestinal mucosa, liver, mesenteric lymph nodes, kidneys and preputial glands. 5. YNK01 was not detected in urine up to 24 hours after dosing. As a major metabolite, 1-β-D-arabinofuranosylcytosine (ara-C) (26.7%) was found. 1-β-D-arabinofuranosyluracil (ara-U) (4.9%) and 1-β-D-arabinofuranosylcytosine 5'-(3-carboxypropyl) phosphate (C-C3 PCA) (1.3%) were found as minor metabolites.