The Allopurinol Hypersensitivity Syndrome: Its Relation to Plasma Oxypurinol Levels
Allopurinol (4-hydroxypyrazolo (3, 4-d)pyrimidine) is a potent inhibitor of uric acid synthesis commonly prescribed for the treatment of gout and other hyperuricemic states (1, 2). Most of the allopurinol is rapidly oxidized to oxypurinol, its major metabolic product (3), which in turn is a potent inhibitor of the enzyme xanthine oxydase. The half-clearance time of oxypurinol is far more prolonged than that of allopurinol (4). Hence, much of the inhibition of uric acid formation and possibly some adverse reactions ascribed to allopurinol may be due to oxypurinol. Pharmacologic studies have indicated that the serum concentration of oxypurinol may be related to the development of life-threatening allopurinol toxicity (5). Thus, it has been suggested that monitorization of plasma oxypurinol levels could prevent unwanted allopurinol effects (6). Recommended plasma oxypurinol concentrations are below 100 μM (7). In fact, no adverse reactions have been described with lower plasma oxypurinol concentrations (5–8). We describe a patient with a severe hypersensitivity reaction to allopurinol who had a plasma oxypurinol concentration of 50 μM.
KeywordsUric Acid Serum Urate Cutaneous Rash Severe Hypersensitivity Reaction HPRT Deficiency
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