URIC ACID METABOLISM IN PATIENTS OF PULMONARY TUBERCULOSIS RECEIVING PZA AND INH

Abstract

Patients receiving PZA showed hyperuricemia and the renal mechanism was found to be involved in this phenomenon. In patients receiving PZA (1.5-3.0gm per day) with the combination of INH (200-300mg per day), the serum level of uric acid rose and reached to a peak in 2 weeks; i.e. from pretreatment level of 3.85(2.0-6.8)mg per dl in mean value to peak value of 8.13(6.0-10.7)mg per dl. The daily output of uric acid fall more rapidly, reaching to a peak value in 1 week which was 296.8(90-552)mg per day in mean value.After 1/2 month, there was no significant change in uric acid serum level and urinary output. In this observation, there was found no significant correlation between these values and the dosis of PZA. In patients treated by PZA, creatinine clearance showed no appreciable change, but uric acid clearance decreased markedly. The urate/creatinine clearance ratio was low that is 0.02-0.04. This may suggest that the reduction of the output of uric acid does not come from the involvement of glomerular mechanism, but from the involvement of tubular mechanism. During PZA-INH treatment, there was no pathological change in N. P. N. and water test.Probenecid (2gm per day) was administered 4 days to the four patients receiving PZA-INH therapy and it was found that the uric acid clearance returned to control level. Probenecid might possess an antagonistic tubular effect to PZA.After stop of the administration of PZA, the serum uric acid of all patients decreased to control level in 7-10 days. So the effect of PZA on tubular function of the kidney is reversible. Also in two patients died after taking long term chemotherapy of PZA (daily 1.5gm and 3.0gm) and INH, the autopsy finding revealed no appreciable change of the kidney. The clinical application of PZA seems to be justified in the relation of its side effect of hyperuricemia and the application of probenecid may have some beneficial effect.