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The effects of administration of drug combinations on uric acid excretion were studied in order to test the hypothesis that a portion of renal tubular reabsorption of uric acid occurs distal to the uric acid secretory site. Oral administration of pyrazinamide (3 g) during probenecid uricosuria (probenecid 500 mg every 6 h) decreased urate excretion from 463 mug/min following probenecid medication alone to 135 mug/min following probenecid plus pyrazinamide (P &lt; 0.01). When a greater uricosuric effect was induced with a 2 g oral dose of probenecid, the decrement in urate excretion which followed pyrazinamide administration (3 g) was more pronounced (2,528 mug/min following probenecid alone, 574 mug/min following probenecid plus pyrazinamide). Results were similar when an 800 mg oral dose of sulfinpyrazone was given in place of probenecid (1,885 mug/min following sulfinpyrazone alone, 475 mug/min following sulfinpyrazone plus pyrazinamide). Thus, apparent urate secretion (measured as the decrease in excretion of urinary uric acid resulting from pyrazinamide administration) appeared to vary, depending upon the degree of inhibition of reabsorption produced by probenecid or sulfinpyrazone. When small doses of aspirin were administered in place of pyrazinamide to produce secretory inhibition, the results were similar. Neither probenecid nor pyrazinamide significantly altered urate excretion when administered to patients with serum salicylate levels above 14 mg/100 ml. These results are interpreted as suggesting that renal tubular reabsorption of uric acid occurs at least in part at a postsecretory site and that a portion of secreted urate is reabsorbed. During maximum probenecid- or sulfinpyrazone-induced uricosuria, inhibition of urate secretion with either pyrazinamide or low doses of aspirin resulted in a decrease in uric acid excretion which exceeded total urinary uric acid during control periods by two- to fourfold. This suggests that renal tubular secretion of urate may greatly exceed uric acid excretion and that a large fraction of secreted urate is reabsorbed. The pyrazinamide suppression test underestimates urate secretion. Uricosuria induced by some drugs, including probenecid, sulfinpyrazone, and iodinated radioopaque dyes, appears to represent, at least in part, inhibition of postsecretory urate reabsorption.

Evidence for a Postsecretory Reabsorptive Site for Uric Acid in Man