Effect of L-dopa on renal handling of uric acid

Several reports have indicated that L-dopa may cause hyperuricemia and gout. The reports of hyperuricemia have generally been explained on the basis that L-dopa is known to produce a false hyperuricemia by interfering in the colorimetric analysis of uric acid. Our studies of the interference of L-dopa in the analysis of uric acid revealed that the false elevation of uric acid produced by therapeutic plasma concentrations of L-dopa is minor. The present studies used the Sperber in vivo chicken technique to determine whether L-dopa interferes with the renal excretion of uric acid. We found that a 440 mg/kg dose of L-dopa given by stomach tube results in a 30% decrease in the renal tubular excretory transport of [14C]uric acid. L-Dopa infused along with [14C]uric acid into the renal portal circulation also decreases the excretory transport of [14C]uric acid. In addition, i.v. L-dopa at 8.5 or 11.6 mumol/min/leg causes an increase in plasma urate of 26 or 45%, respectively. During infusion of L-[14C]dopa into the peritubular circulation, the 14C-label was excreted into the urine at a rate equivalent to 35% that of simultaneously infused p-aminohippuric acid or [3H] tetraethylammonium. The excretory transport of 14C-label was inhibited by probenecid. Because the renal tubular excretory transport of uric acid in chickens has many similarities to that of man, the results suggest that inhibition of uric acid excretory transport may be one of the effects of L-dopa, or its metabolites, in man.