Thiopurinol: Dose-Related Effect on Urinary Oxypurine Excretion
Thiopurinol (mercapto-4-pyrazolo-(3,4-d)pyrimidine) has been shown to effectively reduce both plasma and urinary uric acid levels in the treatment of gout (2,4,5). These effects were observed without showing a concomitant increase in urinary hypoxanthine and xanthine excretion, (2,4,5). As an inhibitor of xanthine oxidase, thiopurinol has been shown to be only one tenth as active as allopurinol in vitro (3). Thiopurinol is ineffective in lowering uric acid levels in gout associated with a deficiency of the enzyme HGPRTase. This observation has led to the suggestion that the drug acts mainly by feedback inhibition of de novo purine synthesis; either by causing an alteration in the balance of available purine nucleotides or by the formation of thiopurinol ribotide (2,5). Extensive metabolic studies have recently been carried out in pigs using 14C allopurinol and 14C thiopurinol (7). These studies revealed no measurable tissue incorporation of either drug and showed that thiopurinol was less well absorbed than allopurinol when administered orally.
KeywordsXanthine Oxidase Uric Acid Level Purine Metabolism Orotic Acid Xanthine Oxidase Activity
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