Intrapulmonary concentrations of pyrazinamide

The objective of this study was to compare the steady state plasma and intr apulmonary concentrations of orally administered pyrazinamide in normal vol unteers and subjects with AIDS, Pyrazinamide was administered at 1 g once d aily for 5 days to 40 adult volunteers (10 men with AIDS, 10 normal men, 10 women with AIDS, and 10 normal women). Subjects with AIDS and with more th an four stools per day were excluded. Blood was obtained prior to administr ation of the first dose, 2 h after the last dose, and at the completion of bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Standardized bronchoscopy was performed without systemic sedati on, The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method. The total number of alveolar cells (AC) was coun ted in a hemocytometer, and differential cell counting was performed after cytocentrifugation, Pyrazinamide was measured by high-performance liquid ch romatography. The presence of AIDS or gender had no significant effect on t he concentrations of pyrazinamide in plasma. The concentrations of pyrazina mide in ELF and AC were lower in the subjects,vith AIDS than in the subject s without AIDS, but the difference was not significant. The concentrations in plasma (mean +/- standard deviation) were 25.1 +/- 7.6 and 21.1 +/- 6.8 mu g/ml at 2 and 4 h after the last dose, respectively, and were not signif icantly different from the concentration (17.4 +/- 16.9 mu g/ml) in AC, The concentration of pyrazinamide in ELF was high (431 +/- 220 mu g/ml) and wa s approximately 4 to 40 times the reported MIC for pyrazinamide-susceptible strains of Mycobacterium tuberculosis. The high concentration of pyrazinam ide in ELF may contribute in part to the effectiveness of the drug in treat ing pulmonary tuberculosis.