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Treatment of gout and urate calculi with allopurinol

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Abstract

ALLOPURINOL is a potent inhibitor of the enzyme xanthine oxidase; it is an isomer of hypoxanthine, the carbon and nitrogen atoms at the seventh and eighth positions of the purine ring being exchanged. The action of allopurinol is twofold, as an inhibitor and also as a substrate for xanthine oxidase. Since uric acid is formed by the action of xanthine oxidase on xanthine and hypoxanthine (Fig. 1), it follows that inhibition of the enzyme xanthine oxidase results in the formation of less than normal amounts of uric acid. As a result, purine end products are excreted in the three forms: hypoxanthine, xanthine, and uric acid.

The effect of allopurinol in lowering the concentrations of uric acid in serum and in urine was discovered fortuitously by Rundles and associates,1 who sought xanthine oxidase inhibitors to slow the degradation of 6-mercaptopurine (6-MP). As a result of the blockage of xanthine oxidase, the conversion of 6-MP to thiouric acid is reduced, and the cytotoxic and immunosuppressive effects of 6-MP and other 6-substituted purines are enhanced several fold.2 However, it is not in the field of antitumor therapy that allopurinol has been primarily useful, but rather in its ability to decrease the production of uric acid.3

In a continuing study, now in its third year, we are following the progress of 20 patients’ disorders of uric acid metabolism whose case data we have previously reported.4 These patients were initially selected from a larger group treated with allopurinol for two reasons: firstly, the patients had . . .


 

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