RT Journal Article SR Electronic T1 DISPOSITION AND METABOLISM OF THIOPURINES JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 645 OP 652 VO 1 IS 4 A1 TI LI LOO A1 KATHERINE LU A1 JEFFREY A. GOTTLIEB YR 1973 UL http://dmd.aspetjournals.org/content/1/4/645.abstract AB 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. Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics