Observations on the reduction of the renal elimination of urate in man caused by the administration of pyrazinamide.

The urinary excretion of pyrazinamide, pyrazinoic acid, 5-hydroxypyrazinoic acid and uric acid were determined in a healthy subject after giving single or multiple doses of pyrazinamide or its metabolite pyrazinoic acid. The results obtained demonstrated that 5-hydroxypyrazinoic acid is a major metabolite of pyrazinoic acid in man and supported previous evidence indicating that the retention of uric acid caused by the administration of pyrazinamide is mediated by pyrazinoic acid. After giving 3 g pyrazinamide the urinary excretion of uric acid was maximally suppressed for 24 hours and partially reduced for a further 24 hours. Prolonged exposure to pyrazinoic acid resulted in a net reduction in the urinary excretion of uric acid. The findings suggested that the degree of uric acid retention in patients treated with pyrazinamide-containing regimens could be reduced by giving pyrazinamide intermittently.