The Effect of Dietary Protein on the Clearance of Allopurinol and Oxypurinol

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Abstract
A decrease in dietary protein is known to depress renal plasma flow and creatinine clearance. Using a randomized crossover design, we investigated the pharmacokinetics of allopurinol and its principal metabolite, oxypurinol, after oral administration of 600 mg of allopurinol in six normal subjects receiving a high-protein (268 g per day) or low-protein (19 g per day) diet. For allopurinol, the area under the curve of plasma concentration versus time increased by a factor of 1.45 (P<0.02), the renal clearance decreased by 28 per cent (P<0.02), and the ratio of the clearance of allopurinol to that of creatinine (fractional excretion) was unchanged between the low-protein and high-protein diets. For oxypurinol, the area under the curve increased nearly threefold (P<0.02), the renal clearance decreased by 64 per cent (P<0.02), the fractional excretion decreased by 49 per cent (P<0.02), and the plasma oxypurinol half-life increased nearly threefold from 17.3±1.5(mean ±S.E.M.) to 49.9±2.9 hours (P<0.02) during the low-protein diet, as compared with the high-protein diet. We conclude that with the low-protein diet, the absorption, metabolism, and excretion of allopurinol were minimally altered but the total-body clearance of oxypurinol was greatly reduced because of a large increase in the net renal tubular reabsorption of oxypurinol. (N Engl J Med 1985; 313: 771–6.)

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