Metabolic studies of high doses of allopurinol in humans

In animals and in humans given high doses of allopurinol, the oxidation of allopurinol to oxipurinol is inhibited, resulting in a higher proportion of unchanged allopurinol and of allopurinol riboside in plasma and urine than is seen at low doses. The dose which produces this inhibition of allopurinol oxidation is higher in rodents than in man or in the dog. Urinary orotate and orotidine increased in proportion to the dose of allopurinol. These increased levels of orotate would be expected to compete more effectively with 5-fluorouracil for conversion to a nucleotide by orotate phosphoribosyltransferase. Since allopurinol and allopurinol riboside are active against leishmaniae in vitro, it may be possible to attain therapeutic levels of allopurinol and allopurinol riboside in vivo by using high doses of allopurinol.