Abstract
The metabolic disposition of allopurinol [4-hydroxypyrazolo(3,4-d)-pyrimidine) was determined in mice, dogs, and human subjects. The drug is a substrate for, as well as an inhibitor of, xanthine oxidase and is converted in all species to the corresponding xanthine analog, alloxanthine, which is its major metabolite. Neither is bound to human plasma proteins, and both are distributed more or less equally in total body water in the mouse. Both analogs are cleared rapidly by the mouse and dog kidney. In the human subject allopurinol is cleared rapidly, but alloxanthine resembles uric acid in having a slow clearance responsive to probenecid. The accumulation of alloxanthine during prolonged therapy with allopurinol may contribute significantly to the therapeutic effects of the drug in the control of hyperuricemias.
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