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Pharmacology

Effects of AIDS and Gender on Steady-State Plasma and Intrapulmonary Ethionamide Concentrations

John E. Conte Jr., Jeffrey A. Golden, Mari McQuitty, Juliana Kipps, Emil T. Lin, Elisabeth Zurlinden
John E. Conte Jr.
Infectious Diseases Research Laboratory, Department of Epidemiology and Biostatistics,and
Departments of Medicine and
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Jeffrey A. Golden
Departments of Medicine and
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Mari McQuitty
Infectious Diseases Research Laboratory, Department of Epidemiology and Biostatistics,and
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Juliana Kipps
Infectious Diseases Research Laboratory, Department of Epidemiology and Biostatistics,and
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Emil T. Lin
Biopharmaceutical Sciences, University of California, San Francisco, San Francisco, California 94143-0208
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Elisabeth Zurlinden
Infectious Diseases Research Laboratory, Department of Epidemiology and Biostatistics,and
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DOI: 10.1128/AAC.44.5.1337-1341.2000
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ABSTRACT

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 μg/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 μg/ml) (P < 0.05). The concentration of ethionamide was significantly greater in ELF (5.63 ± 3.8 μg/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.

  • Copyright © 2000 American Society for Microbiology
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Effects of AIDS and Gender on Steady-State Plasma and Intrapulmonary Ethionamide Concentrations
John E. Conte Jr., Jeffrey A. Golden, Mari McQuitty, Juliana Kipps, Emil T. Lin, Elisabeth Zurlinden
Antimicrobial Agents and Chemotherapy May 2000, 44 (5) 1337-1341; DOI: 10.1128/AAC.44.5.1337-1341.2000

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Effects of AIDS and Gender on Steady-State Plasma and Intrapulmonary Ethionamide Concentrations
John E. Conte Jr., Jeffrey A. Golden, Mari McQuitty, Juliana Kipps, Emil T. Lin, Elisabeth Zurlinden
Antimicrobial Agents and Chemotherapy May 2000, 44 (5) 1337-1341; DOI: 10.1128/AAC.44.5.1337-1341.2000
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KEYWORDS

Acquired Immunodeficiency Syndrome
antitubercular agents
ethionamide
lung
Sex Characteristics

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