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 excretion of filtered urate, then the uricosuric responses (the increment in urate excretion or clearance) should have been unaffected by PZA. Defined in this manner, however, uricosuric responses to probenecid and chlorothiazide were significantly decreased after PZA pretreatment. In order to determine whether PZA diminished other renal actions of chlorothiazide, changes in sodium and inorganic phosphorus excretion were examined. Chlorothiazide produced equivalent natriuretic and phosphaturic responses after PZA pretreatment, indicating that PZA does not interfere with at least some of the renal actions of chlorothiazide. In separate studies, PZA depressed urate excretion by at least 68% during the maintenance of chlorothiazide-induced natriuresis and phosphaturia, suggesting that chlorothiazide does not diminish the anti-secretory action of PZA.
Thomas H. Steele, Geoffrey Boner