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Antimicrobial Agents and Chemotherapy, June 1999, p. 1329-1333, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Intrapulmonary Concentrations of Pyrazinamide

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

Infectious Diseases Research Laboratory, Department of Epidemiology and Biostatistics1 and Department of Medicine,2 University of California, San Francisco, San Francisco, California 94143-0208

Received 14 July 1998/Returned for modification 11 December 1999/Accepted 11 March 1999

The objective of this study was to compare the steady-state plasma and intrapulmonary concentrations of orally administered pyrazinamide in normal volunteers and subjects with AIDS. Pyrazinamide was administered at 1 g once daily for 5 days to 40 adult volunteers (10 men with AIDS, 10 normal men, 10 women with AIDS, and 10 normal women). Subjects with AIDS and with more than four stools per day were excluded. Blood was obtained prior to administration of the first dose, 2 h after the last dose, and at the completion of bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method. The total number of alveolar cells (AC) was counted in a hemocytometer, and differential cell counting was performed after cytocentrifugation. Pyrazinamide was measured by high-performance liquid chromatography. The presence of AIDS or gender had no significant effect on the concentrations of pyrazinamide in plasma. The concentrations of pyrazinamide in ELF and AC were lower in the subjects with AIDS than in the subjects without AIDS, but the difference was not significant. The concentrations in plasma (mean ± standard deviation) were 25.1 ± 7.6 and 21.1 ± 6.8 µg/ml at 2 and 4 h after the last dose, respectively, and were not significantly different from the concentration (17.4 ± 16.9 µg/ml) in AC. The concentration of pyrazinamide in ELF was high (431 ± 220 µg/ml) and was approximately 4 to 40 times the reported MIC for pyrazinamide-susceptible strains of Mycobacterium tuberculosis. The high concentration of pyrazinamide in ELF may contribute in part to the effectiveness of the drug in treating pulmonary tuberculosis.

* Corresponding author. Mailing address: University of California, San Francisco, 350 Parnassus Ave., Ste. 210, San Francisco, CA 94117. Phone: (415) 476-5793. Fax: (415) 476-6612. E-mail: JCONTE{at}AIDS.UCSF.EDU.

Antimicrobial Agents and Chemotherapy, June 1999, p. 1329-1333, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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