This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Conte, J. E.
Right arrow Articles by Zurlinden, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Conte, J. E., Jr.
Right arrow Articles by Zurlinden, E.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2002, p. 2358-2364, Vol. 46, No. 8
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.8.2358-2364.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

John E. Conte Jr.,1,2* Jeffrey A. Golden,2 Mari McQuitty,1 Juliana Kipps,1 Sheila Duncan,1 Elaine McKenna,1 and Elisabeth Zurlinden1

Infectious Diseases Research Laboratory, Department of Epidemiology and Biostatistics,1 Department of Medicine, University of California, San Francisco, San Francisco, California 941172

Received 21 May 2001/ Returned for modification 23 November 2001/ Accepted 17 April 2002

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.

* Corresponding author. Mailing address: Infectious Diseases Research, University of California, San Francisco, 350 Parnassus Ave., Suite 507, San Francisco, CA 94117. Phone: (415) 476-1312. Fax: (415) 476-0760. E-mail: jconte{at}aids.ucsf.edu.

Antimicrobial Agents and Chemotherapy, August 2002, p. 2358-2364, Vol. 46, No. 8
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.8.2358-2364.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kiem, S., Schentag, J. J. (2008). Interpretation of Antibiotic Concentration Ratios Measured in Epithelial Lining Fluid. Antimicrob. Agents Chemother. 52: 24-36 [Full Text]  
  • Conte, J. E. Jr., Golden, J. A., Kipps, J., McIver, M., Zurlinden, E. (2004). Intrapulmonary Pharmacokinetics and Pharmacodynamics of Itraconazole and 14-Hydroxyitraconazole at Steady State. Antimicrob. Agents Chemother. 48: 3823-3827 [Abstract] [Full Text]  
  • Conte, J. E. Jr., Golden, J. A., Kipps, J., Zurlinden, E. (2004). Steady-State Plasma and Intrapulmonary Pharmacokinetics and Pharmacodynamics of Cethromycin. Antimicrob. Agents Chemother. 48: 3508-3515 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»