Metabolic Studies of High Doses of Allopurinol in Humans

Abstract

Allopurinol has been used for 16 years at doses ranging from 200 to 800 mg/day for the control of primary and secondary hyperuricemia. At the most commonly used doses of allopurinol (300–400 mg/ day) about 70% of the allopurinol is oxidized to oxipurinol, which is excreted in the urine. Urinary allopurinol and allopurinol riboside each account for about 10% of the dose. Since the degree of xanthine oxidase inhibition is dose-related, not only the oxidation of hypoxanthine and xanthine to uric acid, but also the oxidation of allopurinol to oxipurinol might be expected to be strongly inhibited at high doses of allopurinol. This would lead to increased levels of allopurinol, as well as allopurinol riboside, in plasma and urine. The extent to which this phenomenon occurs was investigated in several laboratory animal species and in man.