NDLI: Effects of Gender, AIDS, and Acetylator Status on Intrapulmonary Concentrations of Isoniazid

Content Provider	PubMed Central
Author	Conte Jr., John E. Golden, Jeffrey A. Mcquitty, Mari Kipps, Juliana Duncan, Sheila Mckenna, Elaine Zurlinden, Elisabeth
Copyright Year	2002
Abstract	The objective of the present study was to evaluate the effects of gender, AIDS, and acetylator status on the steady-state concentrations of orally administered isoniazid in plasma and lungs. Isoniazid was administered at 300 mg once daily for 5 days to 80 adult volunteers. Subjects were assigned to eight blocks according to gender, presence or absence of AIDS, and acetylator status. Blood was obtained prior to administration of the first dose, 1 h after administration of the last dose, and at the completion of bronchoscopy and bronchoalveolar lavage (BAL), which was performed 4 h after administration of the last dose. The metabolism of caffeine was used to determine acetylator status. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method. Isoniazid concentrations in plasma, BAL fluid, and alveolar cells (ACs) were measured by high-performance liquid chromatography. AIDS status or gender had no significant effect on the concentrations of isoniazid in plasma at 1 or 4 h. Concentrations in plasma at 4 h and concentrations in ELF were greater in slow acetylators than fast acetylators. The concentration in plasma (1.85 ± 1.60 μg/ml [mean ± standard deviation; n = 80]) at 1 h following administration of the last dose was not significantly different from that in ELF (2.25 ± 3.50 μg/ml) or ACs (2.61 ± 5.01 μg/ml). For the entire study group, concentrations in plasma at 1 h were less than 1.0, 2.0, and 3.0 μg/ml for 34.7, 60, and 82.7% of the subjects, respectively; concentrations in ELF were less than 1.0, 2.0, and 3.0 μg/ml in 30 (37.5%), 53 (66.0%), and 58 (72.5%) of the subjects, respectively; and concentrations in ACs were less than 1.0, 2.0, and 3.0 μg/ml in 43 (53.8%), 59 (73.8%), and 65 (81.3%) of the subjects, respectively. The concentrations of orally administered isoniazid in plasma were not affected by gender or the presence of AIDS. The concentrations in plasma at 4 h and the concentrations in ELF, but not the concentrations in ACs, were significantly greater in slow acetylators than fast acetylators. Concentrations in plasma and lungs were low compared to recommended therapeutic concentrations in plasma and published MICs of isoniazid for Mycobacterium tuberculosis. The optimal concentrations of isoniazid in ACs and ELF are unknown, but these data suggest that the drug enters these compartments by passive diffusion and achieves concentrations similar to those found in plasma.
Related Links	http://dx.doi.org/10.1128/AAC.46.8.2358-2364.2002
Starting Page	2358
File Format	PDF
ISSN	10986596
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	8
Volume Number	46
Language	English
Publisher	American Society for Microbiology
Publisher Date	2002-08-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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