Effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol.
نویسندگان
چکیده
The effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol were investigated. Pyrazinamide decreased the mean (SEM) fractional clearance of oxypurinol from 19.2 (2.1) to 8.8 (1.5). Probenecid increased the fractional clearance of oxypurinol from 14.1 (3.5) to 24.8 (4.1). Benzbromarone increased the fractional clearance of oxypurinol from 15.6 (2.3) to 33.8 (2.8). These results suggest that oxypurinol may be secreted by 'an organic acid system' and that oxypurinol is reabsorbed at a putative postsecretory site of the renal tubules.
منابع مشابه
Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion.
Renal hypouricemia is an inherited and heterogeneous disorder characterized by increased urate clearance (CUA). The authors recently established that urate was reabsorbed via URAT1 on the tubular apical membrane and that mutations in SLC22A12 encoding URAT1 cause renal hypouricemia. This study was undertaken to elucidate and correlate clinical and genetic features of renal hypouricemia. The SLC...
متن کاملEvidence for a postsecretory reabsorptive site for uric acid in man.
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 medicati...
متن کاملInvolvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone.
Benzbromarone has been reported to increase the renal clearance of oxypurinol, an active metabolite of allopurinol. We examined the renal transport of oxypurinol to determine whether such a change in renal clearance could be explained by altered transporter-mediated reabsorption. Since the first step of reabsorption takes place at the renal epithelial apical membrane, we focused on membrane tra...
متن کاملOrigins of the uricosuric response.
The acute effects of intravenous (i.v.) probenecid and chlorothiazide on renal urate handling were investigated in paired studies in normal men. Uricosuric responses to these agents were compared in the same subjects, both without and with pyrazinamide (PZA) pretreatment. Assuming that PZA selectively inhibits the tubular secretion of urate and that uricosuric agents act by increasing the excre...
متن کاملErratum to: Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney
BACKGROUND Excess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target ...
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ورودعنوان ژورنال:
- Annals of the rheumatic diseases
دوره 50 9 شماره
صفحات -
تاریخ انتشار 1991