Effects of AIDS and gender on steady-state plasma and intrapulmonary ethionamide concentrations

Ethionamide, 250 mg every 12 h for a total of nine doses, was administered to 40 adult volunteers (10 men with AIDS, 10 healthy men, 10 women with AID S, and 10 healthy women). Blood was obtained for drug assay prior to admini stration of the first dose, 2 h after the last dose, and at the completion of standardized bronchoscopy and bronchoalveolar lavage, which mere perform ed 4 h after the last dose. Ethionamide was measured in epithelial lining f luid (ELF) and alveolar cells (AC) using a new mass spectrometric method. T he presence of AIDS or gender was without significant effect on the concent rations of ethionamide in plasma, AC, or ELF. Plasma concentrations (mean /- standard deviation [SD]) were 0.97 +/- 0.65 and 0.65 +/- 0.35 mu g/ml at 2 and 4 h after the last dose, respectively, and both values were signific antly greater than the concentration of ethionamide in AC (0.38 +/- 0.47 mu g/ml) (P < 0.05). The concentration of ethionamide was significantly great er in ELF (5.63 +/- 3.8 mu g/ml) than in AC or plasma at 2 and 4 h and was approximately 10 to 20 times the reported MIC for ethionamide-susceptible s trains of Mycobacterium tuberculosis. For all 40 subjects, the ELF/plasma c oncentration ratios (mean +/- SD) at 2 and 4 h were 8.7 +/- 11.7 and 9.7 +/ - 5.6, respectively. We conclude that the absorption of orally administered ethionamide, as measured in this study, was not affected by gender or the presence of AIDS. Ethionamide concentrations mere significantly greater in ELF than in plasma or AC, suggesting that substantial antimycobacterial act ivity resides in this compartment.