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Antimicrob Agents Chemother. 2000 May;44(5):1337-41.

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

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Infectious Diseases Research Laboratory, Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94143-0208, USA.


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 AIDS, and 10 healthy women). Blood was obtained for drug assay prior to administration of the first dose, 2 h after the last dose, and at the completion of standardized bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Ethionamide was measured in epithelial lining fluid (ELF) and alveolar cells (AC) using a new mass spectrometric method. The presence of AIDS or gender was without significant effect on the concentrations of ethionamide in plasma, AC, or ELF. Plasma concentrations (mean +/- standard deviation [SD]) were 0.97 +/- 0.65 and 0.65 +/- 0.35 microg/ml at 2 and 4 h after the last dose, respectively, and both values were significantly greater than the concentration of ethionamide in AC (0.38 +/- 0.47 microg/ml) (P < 0. 05). The concentration of ethionamide was significantly greater in ELF (5.63 +/- 3.8 microg/ml) than in AC or plasma at 2 and 4 h and was approximately 10 to 20 times the reported MIC for ethionamide-susceptible strains of Mycobacterium tuberculosis. For all 40 subjects, the ELF/plasma concentration 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 were significantly greater in ELF than in plasma or AC, suggesting that substantial antimycobacterial activity resides in this compartment.

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