Inhibition of urate excretion by pyrazinoate: a micropuncture study

Anesthetized monkeys (Cebus albifrons) undergoing moderate mannitol diuresis were treated with infusions containing lithium urate to elevate the urate concentration in plasma to 45-68 mug/ml and containing the uricosuric drug, 2-nitroprobenecid, to enhance the renal clearance or urate. The urate/inulin clearance ratio was 0.55 +/- 0.03. When pyrazinoate was added to the infusion the clearance ratio fell to 0.26 +/- 0.02. Analysis of free-flow micropuncture samples revealed a major effect of pyrazinoate in the proximal tubule, although an additional, smaller action in the distal tubule could not be definitely excluded. When droplets containing [14C]urate and [3H]inulin were streaked on the surface of the left kidney more urate than inulin appeared in the urine from that kidney (but not the other) within the first 3 min after application. This "excess" excretion of urate could be largely eliminated by pretreatment with pyrazinoate. The results suggest that pyrazinoate inhibits secretion of urate in the proximal tubule.