Sustained reductions in oxipurinol renal clearance during a restricted diet

The renal clearance of oxipurinol, the major metabolite of allopurinol, was studied in six healthy subjects during normal and restricted (low protein and low calorie) diets. A 600 mg oral dose of allopurinol was administered after 7 days of a normal diet (100 mg protein/day) and again after 2 and 4 weeks of a restricted diet (19 gm protein/day). The renal clearance of oxipurinol was reduced from 19.6 +/- 1.5 ml/min during the normal diet to 10.9 +/- 0.8 and 12.0 +/- 0.9 ml/min (both P less than 0.001) during the restricted diet at 2 and 4 weeks, respectively. These changes in oxipurinol renal clearance paralleled changes in uric acid renal clearance. Furthermore, the plasma oxipurinol half-life was increased from 27.0 +/- 1.7 hours during the normal diet to 51.1 +/- 4.3 and 45.7 +/- 3.7 hours (both P less than 0.001) during the restricted diet at 2 and 4 weeks, respectively. We conclude that dietary protein and calorie restriction cause a sustained reduction in the elimination of oxipurinol.