Endogenous production of uric acid

Excessive purine catabolism results in the production of hypoxanthine and xanthine, which are metabolized to uric acid via the enzymatic action of XO. This pathway can be blocked by the use of allopurinol, a hypoxanthine analog that competitively inhibits XO, and febuxostat, a non-purine thiazolecarboxylic acid derivative that selectively inhibits XO. After about two to three days, allopurinol and febuxostat result in increased excretion of both hypoxanthine, which is more soluble than uric acid, and xanthine, which is less soluble than uric acid. Preformed uric acid is not altered by allopurinol or febuxostat. UO, present in most mammals but not humans, oxidizes preformed uric acid to allantoin, which is 5 to 10 times more soluble than uric acid in acid urine. When exogenous UO (uricase, rasburicase, pegloticase) is administered, serum and urinary uric acid levels decrease markedly within approximately four hours.