The effect of dietary protein on the clearance of allopurinol and oxypurinol

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 less than 0.02), the renal clearance decreased by 28 per cent (P less than 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 three-fold (P less than 0.02), the renal clearance decreased by 64 per cent (P less than 0.02), the fractional excretion decreased by 49 per cent (P less than 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 less than 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.