Abstract

Pharmacological disposition of the new antineoplastic agent arabinosyl-6-mercaptopurine has been compared with ribosyl-6-mercaptopurine in dogs and man by means of ³⁵S-labeling. In dogs, after intravenous injection of either drug, the plasma half-time of ³⁵S is about 60 min and the 5-hr cumulative urinary excretion of total radioactivity is 50-70% of the dose. In man the average plasma half-time of ara-MP¹ and metabolites is 101 min, while that of MPR and metabolites is 43 min. The average 24-hr cumulative urinary excretion of ³⁵S is nearly the same: 94% of the injected ara-MP-³⁵S and 91% of the injected MPR-³⁵S. The configuration of the 2'-hydroxyl group of these two drugs confers gross dissimilarities in their biotransformation in both species. Ara-MP is excreted mostly unchanged; there is neither cleavage nor oxidation. S-Methylation of ara-MP has, however, been established by the identification of arabinosyl-6-methylthiopurine as one of the minor metabolites. In contrast, MPR undergoes extensive catabolism to 6-mercaptopurine, its oxidized products, and other minor metabolites. S-Methylation of MPR has nevertheless not been observed.