Skip Navigation



JAC Advance Access published online on May 7, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn187
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
62/1/161    most recent
dkn187v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Dickinson, L.
Right arrow Articles by Back, D. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dickinson, L.
Right arrow Articles by Back, D. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing

Laura Dickinson1,*, Marta Boffito2, Saye H. Khoo1, Malte Schutz3, Leon J. Aarons4, Anton L. Pozniak2 and David J. Back1

1 Department of Pharmacology, University of Liverpool, Liverpool, UK 2 PK Research Ltd, St Stephen's Centre, Chelsea and Westminster Foundation Trust, London, UK 3 Roche Pharmaceuticals, Nutley, NJ, USA 4 School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK

Received 6 January 2008; returned 25 March 2008; revised 27 March 2008; accepted 3 April 2008

* Corresponding author. Tel: +44-151-794-5553; Fax: +44-151-794-5656; E-mail: laurad{at}liv.ac.uk

Objectives: One potential concern of once-daily protease inhibitor administration is low trough concentrations and ultimately the ‘forgiveness’ or robustness in comparison with the originally licensed twice-daily dose. To give an estimation of ‘forgiveness’, we determined the length of time plasma drug concentrations were below target in HIV-infected patients receiving saquinavir/ritonavir regimens.

Methods: Seventy-seven pharmacokinetic profiles (saquinavir/ritonavir 1000/100 mg twice daily, n = 34; 1600/100 mg once daily, n = 26; 2000/100 mg once daily, n = 17) from five studies were combined, presented as twice- and once-daily percentiles (P10–P90) and compared. At percentiles where trough concentrations fell below the alleged minimum effective concentration (MEC; 100 ng/mL), the length of time below MEC was determined.

Results: Saquinavir concentrations were below MEC at P10 for 0.7 h for twice-daily saquinavir/ritonavir when compared with 8.6 and 6.6 h for 1600/100 and 2000/100 mg once daily, respectively. At P25, 1600/100 mg once daily produced suboptimal concentrations for 5.5 h in contrast to 0.5 h for 2000/100 mg once daily.

Conclusions: Here, we provide substantive data that indicate once-daily saquinavir, in particular 1600/100 mg, is not as robust as the twice-daily regimen based on a population of UK patients; this raises concern over late or missed doses. However, pharmacokinetic data can only ever be a guide to the impact on long-term efficacy.

Key Words: HIV , pharmacokinetics , once daily , robustness


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.