Diamond H S, Paolino J S
J Clin Invest. 1973 Jun;52(6):1491-9. doi: 10.1172/JCI107323.
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 < 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.
为了验证尿酸的部分肾小管重吸收发生在尿酸分泌部位远端这一假说，研究了联合用药对尿酸排泄的影响。在丙磺舒促尿酸尿期间（丙磺舒500mg，每6小时一次）口服吡嗪酰胺（3g），可使尿酸排泄量从单用丙磺舒时的463μg/min降至丙磺舒加吡嗪酰胺后的135μg/min（P<0.01）。当口服2g丙磺舒诱导出更大的促尿酸尿作用时，吡嗪酰胺（3g）给药后尿酸排泄量的减少更为明显（单用丙磺舒时为2528μg/min，丙磺舒加吡嗪酰胺后为574μg/min）。当用800mg口服剂量的磺吡酮替代丙磺舒时，结果相似（单用磺吡酮时为1885μg/min，磺吡酮加吡嗪酰胺后为475μg/min）。因此，表观尿酸分泌（以吡嗪酰胺给药导致的尿尿酸排泄减少来衡量）似乎有所不同，这取决于丙磺舒或磺吡酮对重吸收的抑制程度。当用小剂量阿司匹林替代吡嗪酰胺以产生分泌抑制时，结果相似。当给血清水杨酸盐水平高于14mg/100ml的患者使用丙磺舒或吡嗪酰胺时，二者均未显著改变尿酸排泄。这些结果被解释为提示尿酸的肾小管重吸收至少部分发生在分泌后部位，且一部分分泌的尿酸被重吸收。在丙磺舒或磺吡酮诱导的最大促尿酸尿期间，用吡嗪酰胺或低剂量阿司匹林抑制尿酸分泌会导致尿酸排泄减少，其减少量比对照期的总尿尿酸量高出两到四倍。这表明尿酸的肾小管分泌可能大大超过尿酸排泄，且大部分分泌的尿酸被重吸收。吡嗪酰胺抑制试验低估了尿酸分泌。包括丙磺舒、磺吡酮和碘化造影剂在内的一些药物诱导的促尿酸尿，似乎至少部分代表了对分泌后尿酸重吸收的抑制。
