Acute and chronic studies were performed on 6 bealthy human volunteers. Four subjects took a Single oral dose of tienilic acid 1,000 mg. A week later, the same subjects took pyrazinamide (PZA) orally 3 g 90 min prior to the ingestion of the same dose of tienilic acid. Following tienilic acid alone, a marked uricosuric effect lasting at least 8 h was noted, the ratio of urate clearance over endogenous Creatinine clearance (Cur/Ccr) reaching 0.55. At the same time, plasma urate feil from 6.8 to 2.7 mg%. After PZA, the uricosuric response to tienilic acid was only slightly depressed during the first 4 h. However, the blunting effect became more important during the next 20 h. During the chronic studies tienilic acid (250–500 mg/day) was administered during 7 days to 6 subjects maintained on a constant diet. In these studies Cur/Ccr rose from 0.11 to 0.25 while plasma urate decreased from 6.0 to 3.0 mg%. Hydrochlorothiazide administered in equivalent dosage (50–100 mg/day) induced a fall in Cur/Ccr from 0.09 to 0.05. This was accompanied by a significant rise in plasma urate from 6.3 to 7.8 mg%. Cumulative increase in urinary sodium excretion after 7 days was slightly higher with hydrochlorothiazide than with tienilic acid. Total body loss averaged 1.9 kg with tienilic acid and 2.2 kg with hydrochlorothiazide. However, in contrast to hydrochlorothiazide, the cumulative increase in potas-sium excretion was much greater with tienilic acid and serum potassium feil from 4.0 to 3.4 mEq/1. At the same time net urinary hydrogen ion excretion rose markedly and was accompanied by the development of moderate metabolic alkalosis serum bicarbonate rising from 26.5 to 34.2 mEq/1. Tienilic acid had a definite hypocalciuric effect. However, the latter was less important than that induced with hydrochlorothiazide. Tienilic acid, a new diuretic, appears to be a potent uricosuric agent in normal man when administered on an acute or a chronic basis. In spite of a moderate natriuretic effect, it exerts a marked action on both potassium and net acid excretion with resulting hypokalemia and metabolic alkalosis.

Keywords:
Tienilic acid, Diuretics, Urate excretion, Hypouricemia, Metabolie alkalosis, Hypokalemia
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© 1978 S. Karger AG, Basel
1978
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