Comparative study of cyclocytidine and arabinosylcytosine disposition in rats.

The stability of cyclocytidine (II) in aqueous solutions decreased with increasing pH and temperature. After intravenous injection to rats the biphasic decline of cyclocytidine in the serum was accompanied by simultaneous formation of arabinosylcytosine. Since under physiological conditions (37 degrees C, pH 7.2) the half-lifetime of cyclocytidine dissolved in water was 5 hours, the very early appearance of arabinosylcytosine in the serum of rats suggests that various hydrolytic enzymes may also be responsible for the conversion of cyclocytidine in to arabinosylcytosine in vivo. An equimolar dose of arabinosylcytosine (I) injected to rats produced serum levels which were several times higher than those of cyclocytidine under the same conditions. Since the rate constant of overall elimination was similar for both compounds, this difference in serum levels may most probably be explained by a much higher distribution volume of cyclocytidine resulting also in a higher plasmatic clearance of this compound.