Skip Navigation


BJA Advance Access originally published online on June 11, 2008
British Journal of Anaesthesia 2008 101(2):186-193; doi:10.1093/bja/aen147
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
101/2/186    most recent
aen147v1
Right arrow E-Letters: Submit a response to the article
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
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 Ravenelle, F.
Right arrow Articles by Smith, D. C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ravenelle, F.
Right arrow Articles by Smith, D. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


© The Board of Management and Trustees of the British Journal of Anaesthesia 2008. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Anaesthetic effects of propofol polymeric micelle: a novel water soluble propofol formulation

F. Ravenelle1,*, P. Vachon2, A. E. Rigby-Jones3, J. R. Sneyd3, D. Le Garrec1, S. Gori1, D. Lessard1 and D. C. Smith1

1 Labopharm Inc., 480 Blvd. Armand-Frappier, Laval, Québec, Canada H7V 4B4
2 Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, University of Montreal, CP 5000, Saint-Hyacinthe, Québec, Canada J2S 7C6
3 Peninsula College of Medicine and Dentistry, The John Bull Building, Research Way, Tamar Science Park, Plymouth PL6 8BU, UK

* Corresponding author. E-mail: fravenelle{at}labopharm.com

Background: As a result of its very low water solubility, propofol is generally presented as a lipid-based formulation with well-characterized limitations.

Methods: Propofol (99.7%) was added directly to an aqueous solution of poly(N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide)copolymers (PVP-PLA) block copolymers and stirred in order to obtain a clear solution. This formulation was filtered sterile and then lyophilized to its solid form Propofol-PM (propofol polymeric micelle) which reconstitutes to a propofol 1%w/v (10 mg ml–1) clear aqueous solution of 30–60 nm propofol-containing micelles. Population pharmacokinetic data from whole blood and plasma were obtained by administering reconstituted Propofol-PM formulations and a 1% oil in water formulation, Diprivan® to male Sprague–Dawley rats (n = 40) at a dose of 10 mg kg–1. Preliminary recovery data were obtained from a further small study.

Results: The pharmacokinetics were best described using a two-compartment mamillary population model, which incorporated sample matrix (blood or plasma) and propofol formulation (Diprivan® or Propofol-PM) as covariates. Sample matrix was applied to all structural model parameters as a dichotomous covariate. An influence of propofol formulation was observed for all parameters (excluding distributional clearance) but only when plasma was used for propofol quantification. In this preliminary pharmacodynamic study, there was no statistically significant difference in the timing of the recovery endpoints between the Propofol-PM formulation and Diprivan® groups.

Conclusions: Propofol-PM formulations produce anaesthesia in rats. Whole blood pharmacokinetics of Propofol-PM did not differ from those observed with Diprivan®.

Keywords: anaesthetics i.v, propofol; copolymer; formulations, polymeric micelles; pharmacodynamics; pharmacokinetics, propofol


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.