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Antimicrobial Agents and Chemotherapy, April 2000, p. 985-990, Vol. 44, No. 4
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Single-Dose Intrapulmonary Pharmacokinetics of Rifapentine in Normal Subjects

John E. Conte Jr.,1,2,3,* Jeffrey A. Golden,2 Mari McQuitty,1 Juliana Kipps,1 Emil T. Lin,4 and Elisabeth Zurlinden1

Infectious Diseases Research Laboratory, Department of Epidemiology & Biostatistics,1 and Departments of Medicine,2 Microbiology & Immunology,3 and Biopharmaceutical Sciences,4 University of California, San Francisco, San Francisco, California 94117

Received 12 May 1999/Returned for modification 18 September 1999/Accepted 10 January 2000

The intrapulmonary pharmacokinetics of rifapentine were studied in 30 volunteers who received a single, oral dose of rifapentine (600 mg). Subgroups of five subjects each underwent bronchoscopy and bronchoalveolar lavage (BAL) at timed intervals following drug administration. Drug concentrations, including the concentration of the primary metabolite 25-desacetyl rifapentine, were determined in plasma, BAL fluid, and alveolar cells (AC) by high-pressure liquid chromatography. The concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. The concentration-time data were fit to two-compartment (plasma) or one-compartment (AC and ELF) models. The peak concentrations in plasma, ELF, and AC, 26.2, 3.7, and 5.3 µg/ml, respectively, occurred at 5, 5, and 7 h after drug administration, respectively. The half-lives and areas under the curve for plasma, ELF, and AC were 18.3 h and 520 µg · h/ml, 20.8 h and 111 µg · h/ml, and 13.0 h and 133 µg · h/ml, respectively. Although the intrapulmonary rifapentine concentrations were less than the plasma rifapentine concentrations at all time periods, they remained above the proposed breakpoint for M. tuberculosis (0.5 µg/ml) for the 48-h observation period. These data provide a pharmacokinetic rationale for extended-interval dosing. The optimum dosing regimen for rifapentine will have to be determined by controlled clinical trials.

* Corresponding author. Mailing address: University of California, San Francisco, 350 Parnassus Ave., Suite 210, San Francisco, CA 94117. Phone: (415) 476-1312. Fax: (415) 476-6612. E-mail: eveb{at}emailhis.ucsf.edu.

Antimicrobial Agents and Chemotherapy, April 2000, p. 985-990, Vol. 44, No. 4
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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