Study of urinary pyrazinamide metabolites and their action on the renal excretion of xanthine and hypoxanthine in a xanthinuric patient.

A chromatographic technique on anion exchange column was developed. It permets to determine unmetabolized pyrazinamide and three major metabolities: pyrazinoic acid, 5-hydroxypyrazinoic acid and an unidentified compound. In a xanthinuric patient only traces of 5-hydroxypyrazinoic acid were found 12 hours after 3 g pyrazinamide were given. These finding confirms that pyrazinoic acid is oxidised through the the action of xanthine oxidase. Both the clearances of hypoxanthine and of xanthine are as rapid as that of endogenous creatinine in a xanthinuric patient. But the effects of pyrazinamide are different on both purine bases. Urinary excretion of hypoxanthine is slightly but not significantly reduced while excretion of xanthine is decreased by about 75%. Evidence was demonstrated that pyrazinoic acid is likely the agent causing xanthine retention. These results suggest that the mechanisms of renal transport of xanthine and hypoxanthine are different.