1. We have studied the effects of the diuretic tienilic acid (Ticrynafen) upon renal tubular transport of urate, in 11 healthy volunteers on a constant dietary intake.
2. Daily administration of tienilic acid for 10 days to six subjects reduced the mean body weight from 67·1 ± 4·7 kg to 64·5 ± 4·7 kg and a reversible fall in serum urate from a mean value of 0·34 ± 0·04 to 0·16 ± 0·01 mmol/l. Fractional urate excretion in the six subjects on the first day of therapy was 30·3 ± 5·6% and then fell to reach a new steady-state mean value of 17·4 ± 2·0%.
3. To evaluate the mechanism of the uricosuria, studies were performed during acute sustained water diuresis in five subjects to assess the effects of tienilic acid, pyrazinamide, probenecid and their combinations.
4. Fractional urate excretion increased markedly with tienilic acid from 11·2 ± 1·3% to 47·5 ± 5·7%. Pyrazinamide, 24·4 mmol (3 g) orally, decreased urate excretion to 5·1 ± 0·7% and markedly blunted the uricosuric effects but not the 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.
5. We suggest that tienilic acid increased urate excretion by inhibiting reabsorption of both filtered and secreted urate. We have used our results to construct semi-quantitative estimates of the various components of urate transport in man.
