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 Dooley, K.
Right arrow Articles by Dorman, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dooley, K.
Right arrow Articles by Dorman, S. E.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2008, p. 4037-4042, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00554-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Repeated Administration of High-Dose Intermittent Rifapentine Reduces Rifapentine and Moxifloxacin Plasma Concentrations{triangledown}

Kelly Dooley,1,2 Charles Flexner,2 Judith Hackman,1 Charles A. Peloquin,3 Eric Nuermberger,1 Richard E. Chaisson,1 and Susan E. Dorman1*

Divisions of Infectious Diseases,1 Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland,2 Infectious Disease Pharmacokinetics Laboratory, National Jewish Medical and Research Center, Denver, Colorado3

Received 29 April 2008/ Returned for modification 2 August 2008/ Accepted 25 August 2008

Moxifloxacin- and rifapentine-based regimens are under investigation for the treatment of tuberculosis. However, rifapentine may induce enzymes that metabolize moxifloxacin, resulting in decreased moxifloxacin concentrations. In this phase I, two-period, sequential-design study, 13 subjects received 400 mg moxifloxacin daily for 4 days followed by daily moxifloxacin coadministered with 900 mg rifapentine thrice weekly. Pharmacokinetic analyses were performed after the 4th and 19th doses of moxifloxacin and after the 1st and 7th doses of rifapentine. For moxifloxacin, the mean area under the concentration-time curve from 0 to 24 h (AUC0-24) decreased by 17.2% (P = 0.0006) when the drug was coadministered with rifapentine, and the mean half-life (t1/2) decreased from 11.1 to 8.9 h (P = 0.0033). For rifapentine, the mean AUC0-48 after seven thrice-weekly doses decreased by 20.3% (P = 0.0035) compared to the AUC0-48 after the first dose, and the mean t1/2 decreased from 18.5 to 14.8 h (P = 0.0004). The AUC0-48 for the 25-desacetyl-rifapentine metabolite diminished 21%. Two days after completing the study drugs, one subject developed a fever and hepatitis, and another developed a flu-like illness with a rash. In conclusion, rifapentine modestly reduced moxifloxacin concentrations. Changes consistent with rifapentine autoinduction of metabolism were seen. Adverse reactions in two subjects may have represented rifamycin hypersensitivity syndrome, although some features were atypical.

* Corresponding author. Mailing address: Center for Tuberculosis Research, 1550 Orleans Street, Room 1M.08, Johns Hopkins University, Baltimore, MD 21231. Phone: (410) 955-1755. Fax: (410) 955-0740. E-mail: dsusan1{at}jhmi.edu

{triangledown} Published ahead of print on 2 September 2008.

Antimicrobial Agents and Chemotherapy, November 2008, p. 4037-4042, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00554-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • van den Boogaard, J., Kibiki, G. S., Kisanga, E. R., Boeree, M. J., Aarnoutse, R. E. (2009). New Drugs against Tuberculosis: Problems, Progress, and Evaluation of Agents in Clinical Development. Antimicrob. Agents Chemother. 53: 849-862 [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»