THE DISPOSITION OF THE NEW ARABINOSYLCYTOSINE DERIVATIVE - 5'-CHLORO-5'-DEOXY-ARABINOSYLCYTOSINE - IN RATS

1. Pharmacokinetic properties of a new derivative of the widely used a nd very potent antileukemic agent arabinosylcytosine (araC)-5'-chloro- 5'-deoxy-arabinosylcytosine (5'-Cl-araC)-were investigated after intra peritoneal (i.p.) and oral routes of administration in rats and compar ed with the equimolar dose of araC administered orally. 2. It was foun d that substitution of the hydroxyl group at position 5' resulted in a change of pharmacokinetic parameters. 3. There is a large difference in average serum concentrations of 5'-Cl-araC administered by the i.p. and oral routes; the average serum concentration obtained after i.p. injection being several times higher in comparison to those after oral administration. 4. However, the latter are, at the same time, lower t han the average serum concentrations of araC administered by the same route in an equimolar dose. 5. On the other hand, the apparent volume of distribution is much larger, and the area under the curve of serum concentration of 5'-Cl-araC is smaller, after oral as compared to the i.p. route of administration indicating more extensive tissue distribu tion together with higher tissue binding of 5'-Cl-araC when compared t o the parental drug araC.