Abstract

. The ultimate goal of this research is to improve the treatment of tuberculosis in HIV positive and HIV negative patients and to develop new pharmacologic data that will facilitate further tuberculosis research.
The specific aims are to determine and compare: a) the plasma pharmacokinetics of orally administered antituberculous agents, specifically isoniazid, rifampin, pyrazinamide, ethambutol and ethionamide in HIV positive and HIV negative men and women and b) the intrapulmonary pharmacokinetics of the above drugs in the same groups by measuring drug concentrations in bronchoalveolar lavage (BAL) fluid and alveolar cells (AC) and by estimating drug concentrations in pulmonary epithelial lining fluid (ELF). The overall strategy will be to administer one of five anti- tuberculous drugs, i.e. isoniazid, rifampin, pyrazinamide, ethambutol and ethionamide, to healthy subjects and AIDS patients for five days and then, four hours after the last dose, assess the intrapulmonary and plasma concentrations of the drugs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI036054-04
Application #
2607832
Study Section
AIDS and Related Research Study Section 5 (ARRE)
Project Start
1994-12-01
Project End
2000-11-30
Budget Start
1997-12-01
Budget End
2000-11-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Conte, John E; Golden, Jeffrey A; Kipps, Juliana E et al. (2004) Effect of sex and AIDS status on the plasma and intrapulmonary pharmacokinetics of rifampicin. Clin Pharmacokinet 43:395-404
Conte Jr, John E; Lin, Emil; Zhao, Yeping et al. (2002) A high-pressure liquid chromatographic-tandem mass spectrometric method for the determination of ethambutol in human plasma, bronchoalveolar lavage fluid, and alveolar cells. J Chromatogr Sci 40:113-8
Conte Jr, John E; Golden, Jeffrey A; McQuitty, Mari et al. (2002) Effects of gender, AIDS, and acetylator status on intrapulmonary concentrations of isoniazid. Antimicrob Agents Chemother 46:2358-64
Conte Jr, J E; Wang, G; Lin, E T et al. (2001) High-performance liquid chromatographic-tandem mass spectrometric method for the determination of ethionamide in human plasma, bronchoalveolar lavage fluid and alveolar cells. J Chromatogr B Biomed Sci Appl 753:343-53
Conte Jr, J E; Golden, J A; Kipps, J et al. (2001) Effects of AIDS and gender on steady-state plasma and intrapulmonary ethambutol concentrations. Antimicrob Agents Chemother 45:2891-6
Conte Jr, J E; Golden, J A; McQuitty, M et al. (2000) Effects of AIDS and gender on steady-state plasma and intrapulmonary ethionamide concentrations. Antimicrob Agents Chemother 44:1337-41
Conte Jr, J E; Lin, E; Zurlinden, E (2000) High-performance liquid chromatographic determination of pyrazinamide in human plasma, bronchoalveolar lavage fluid, and alveolar cells. J Chromatogr Sci 38:33-7
Conte Jr, J E; Lin, E; Zurlinden, E (2000) Liquid chromatographic determination of rifampin in human plasma, bronchoalveolar lavage fluid, and alveolar cells. J Chromatogr Sci 38:72-6
Conte Jr, J E; Golden, J A; Duncan, S et al. (1999) Intrapulmonary concentrations of pyrazinamide. Antimicrob Agents Chemother 43:1329-33
Delahunty, T; Lee, B; Conte, J E (1998) Sensitive liquid chromatographic technique to measure isoniazid in alveolar cells, bronchoalveolar lavage and plasma in HIV-infected patients. J Chromatogr B Biomed Sci Appl 705:323-9