Mechanisms of the Uricosuric Effect of the Diuretic Tienilic Acid (Ticrynafen) in Man

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Abstract
The effects of the diuretic tienilic acid (Ticrynafen) upon renal tubular transport of urate were studied in 11 healthy volunteers on a constant dietary intake. Daily administration of tienilic acid for 10 days to 6 subjecte reduced mean body weight and caused a reversible fall in serum urate. Fractional ureate excretion in the 6 subjects on the 1st day of therapy was 30.3 .+-. 5.6% and then fell to reach a new steady-state mean value of 17.4 .+-. 2.0%. To evaluate the mechanism of uricosuria, studies were performed during acute sustained water diuresis in 5 subjects to assess effects of tienilic acid, pyrazinamide, probenecid and their combinations. Fractional urate excretion increased markedly with tienilic acid. Pyrazinamide, 24.4 mmol (3 g) orally, decreased urate excretion to 5.1 .+-. 0.7% and markedly blunted uricosuric effects but not natriuresis of tienilic acid. Probenecid increased urate excretion to 26 .+-. 6.0% and when given with tienilic acid increased urate excretion to 66.4 .+-. 2.6%. Addition of pyrazinamide to this combination decreased urate excretion to 19.6 .+-. 4.0%, which was greater than the effect with pyrazinamide alone. Tienilic acid apparently increased urate excretion by inhibiting reabsorption of filtered and secreted urate. Semi-quantitative estimates of various components of urate transport in man were constructed.

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