Concentrations of pyrazinamide attained in serum with different doses of the drug.

Serial concentrations of pyrazinamide in 3 volunteers showed that increasing the dose from 22 mg/kg of body-weight to 66 mg/kg resulted in substantially higher serum concentrations of the drug and a longer period of coverage (at a concentration of 25 mug/ml). Similarly, in a study based on 6 tuberculous patients, increasing the dose of pyrazinamide from 66 mg/kg to 88 mg/kg led to appreciably higher concentrations in the serum. In neither series of tests was any acute hepatic toxicity observed. The findings suggest that it would be interesting to study the effect of doses of about 90 mg/kg of pyrazinamide in once-weekly regimens of chemotherapy for the treatment of tuberculosis.