Pharmacological disposition in mice of o2:2′-anhydro-i-β-d-arabinosylcytosine 3′-phosphate, a potential antileukemic agent

The observation that the cytidine analog, O 2 :2'-anhydro-l-β- D -arabinosylcytosine 3'-phosphate (anhydro-ara-CMP), yields 1-β- D -arabinofuranosylcytosine (ara-C) as a degradation product in vitro , prompted us to investigate the metabolism of [ 14 C]-anhydro-ara-CMP in mice. This study includes measurements of excretory rates and appearance of labeled material in the blood stream, distribution of activity in tissue at specified times, and metabolic assay of degradation products within certain mitotically active tissues. Analysis of both urine and faeces indicates that approximately 40 per cent of the labeled material remains within the animals after 24 hr. Measurement of [ 14 C] activity in the blood gave a peak absorption time at 1 hr after intraperitoneal injections. Reasonable levels of activity in the blood were present even after 72 hr. The metabolic assay of liver and spleen tissue taken at 1 hr showed anhydro-ara-C as the major metabolite, with a significant amount of ara-C and its di- and triphosphates also being formed. Cytidine phosphates were also detected. Single doses of 2000 mg/kg and daily doses of 1000 mg/kg for 5 days caused no fatalities among the test animals.