THE METABOLISM OF 6-CHLOROPURINE-8-C¹⁴ IN THE RAT

¹ Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland

Carbon-labeled 6-chloropurine, when administered parenterally to adult rats is rapidly absorbed and disappears from the blood with a half-time of approximately 1 hour, accumulating to the greatest extent in the liver.

In 24 hours, 5% of administered radioactivity is excreted as carbon dioxide, and 50% in the urine, which contains principally unchanged drug, 6-chlorouric acid, an unknown dehalogenated metabolite, and the normal products of purine catabolism. The presence of the last indicates an appreciable degree of dechlorination in vivo.

The dehalogenated purine skeleton of 6-chloropurine is utilized in the biosynthesis of both RNA and DNA purines. The respective degrees of labeling of nucleic acid adenine and guanine suggest that this utilization proceeds through an anabolic pathway which does not include hypoxanthine as an intermediate.