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 Ruane, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ruane, P. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, February 2007, p. 560-565, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00560-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Plasma Amprenavir Pharmacokinetics and Tolerability following Administration of 1,400 Milligrams of Fosamprenavir Once Daily in Combination with either 100 or 200 Milligrams of Ritonavir in Healthy Volunteers{triangledown}

Peter J. Ruane,1 Andrew D. Luber,1,2* Mary Beth Wire,3 Yu Lou,3 Mark J. Shelton,3 C. Tracey Lancaster,3 Keith A. Pappa,3 COL10053 Study Team

Light Source Medical, Los Angeles, California,1 4 Courtland Drive, Voorhees, New Jersey,2 GlaxoSmithKline, Research Triangle Park, North Carolina3

Received 5 May 2006/ Returned for modification 31 August 2006/ Accepted 30 October 2006

Once-daily (QD) fosamprenavir (FPV) at 1,400 mg boosted with low-dose ritonavir (RTV) at 200 mg is effective when it is used in combination regimens for the initial treatment of human immunodeficiency virus infection. Whether a lower RTV boosting dose (i.e., 100 mg QD) could ensure sufficient amprenavir (APV) concentrations with improved safety/tolerability is unknown. This randomized, two 14-day-period, crossover pharmacokinetic study compared the steady-state plasma APV concentrations, safety, and tolerability of FPV at 1,400 mg QD boosted with either 100 mg or 200 mg of RTV QD in 36 healthy volunteers. Geometric least-square (GLS) mean ratios and the associated 90% confidence intervals (CIs) were estimated for plasma APV maximum plasma concentrations (Cmax), the area under the plasma concentration-time curve over the dosing period (AUC0-{tau}), and trough concentrations (C{tau}) during each dosing period. Equivalence between regimens (90% CIs of GLS mean ratios, 0.80 to 1.25) was observed for the plasma APV AUC0-{tau} (GLS mean ratio, 0.90 [90% CI, 0.84 to 0.96]) and Cmax (0.97 [90% CI, 0.91 to 1.04]). The APV C{tau} was 38% lower with RTV at 100 mg QD than with RTV at 200 mg QD (GLS mean ratio, 0.62 [90% CI, 0.55 to 0.69]) but remained sixfold higher than the protein-corrected 50% inhibitory concentration for wild-type virus, with the lowest APV C{tau} observed during the 100-mg QD period being nearly threefold higher. The GLS mean APV C{tau} was 2.5 times higher than the historical C{tau} for unboosted FPV at 1,400 mg twice daily. Fewer clinical adverse drug events and smaller increases in triglyceride levels were observed with the RTV 100-mg QD regimen. Clinical trials evaluating the efficacy and safety of FPV at 1,400 mg QD boosted by RTV at 100 mg QD are now under way with antiretroviral therapy-naïve patients.

* Corresponding author. Mailing address: 4 Courtland Drive, Voorhees, NJ 08043. Phone: (856) 266-3648. Fax: (856) 784-2730. E-mail: a.luber{at}earthlink.net.

{triangledown} Published ahead of print on 6 November 2006.

Antimicrobial Agents and Chemotherapy, February 2007, p. 560-565, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00560-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ye, Z.-w., Augustijns, P., Annaert, P. (2008). Cellular Accumulation of Cholyl-Glycylamido-Fluorescein in Sandwich-Cultured Rat Hepatocytes: Kinetic Characterization, Transport Mechanisms, and Effect of Human Immunodeficiency Virus Protease Inhibitors. Drug Metab. Dispos. 36: 1315-1321 [Abstract] [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»