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
Google Scholar
Right arrow Articles by la Porte, C. J. L.
Right arrow Articles by Cameron, D. W.
PubMed
Right arrow PubMed Citation
Right arrow Articles by la Porte, C. J. L.
Right arrow Articles by Cameron, D. W.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2009, p. 4840-4844, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00462-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Lack of Effect of Efavirenz on the Pharmacokinetics of Tipranavir-Ritonavir in Healthy Volunteers{triangledown}

C. J. L. la Porte,1* J. P. Sabo,2 L. Béïque,1 and D. W. Cameron1

Ottawa Hospital Research Institute and University of Ottawa, Ottawa, Ontario, Canada,1 Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut2

Received 7 April 2009/ Returned for modification 2 August 2009/ Accepted 21 August 2009

Previously it has been shown that tipranavir-ritonavir (TPV/r) does not affect efavirenz (EFV) plasma concentrations. This study investigates the effect of steady-state EFV on steady-state TPV/r pharmacokinetics. This was a single-center, open-label, multiple-dose study of healthy adult female and male volunteers. TPV/r 500/200 mg twice a day (BID) was given with food for 24 days. After dosing with TPV/r for 10 days, EFV 600 mg once a day was added to the regimen. Intensive pharmacokinetic (PK) sampling was done on days 10 and 24. Validated bioanalytical high-pressure liquid chromatography-tandem mass spectrometry methods were used to determine plasma tipranavir (TPV), ritonavir (RTV), and EFV concentrations. Thirty-four subjects were entered into the study, and 16 subjects completed it. The geometric mean ratios (90% confidence intervals) for TPV and RTV area under the curves, Cmaxs, and Cmins comparing TPV/r alone and in combination with EFV were 0.97 (0.87 to 1.09), 0.92 (0.81 to 1.03), and 1.19 (0.93 to 1.54) for TPV and 1.03 (0.78 to 1.38), 0.92 (0.65 to 1.30), and 1.04 (0.72 to 1.48) for RTV. Frequently observed adverse events were diarrhea, headache, dizziness, abnormal dreams, and rash. EFV had no effect on the steady-state PK of TPV or RTV, with the exception of a 19% increase in the TPV Cmin, which is not clinically relevant. TPV/r can be safely coadministered with EFV and without the need for a dose adjustment.

* Corresponding author. Mailing address: Ottawa Hospital Research Institute, 501 Smyth Road, Mailbox 223, Ottawa, Ontario K1H 8L6, Canada. Phone: (613) 737-8899, ext. 71893. Fax: (613) 737-8696. E-mail: claporte{at}ohri.ca

{triangledown} Published ahead of print on 31 August 2009.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4840-4844, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00462-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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