Anaesthetic effects of propofol polymeric micelle: a novel water soluble propofol formulation.
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.
Labopharm Inc., 480 Blvd. Armand-Frappier, Laval, Québec, Canada H7V 4B4. fravenelle@labopharm.com
F
F
Ravenelle
P
P
Vachon
A E
AE
Rigby-Jones
J R
JR
Sneyd
D
D
Le Garrec
S
S
Gori
D
D
Lessard
D C
DC
Smith
D018686:Anesthetics, Intravenous / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D008823:Micelles; D011137:Polystyrenes; D011145:Polyvinyls; D015742:Propofol / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D012995:Solubility; D014867:Water
D018686:Anesthetics, Intravenous; D008823:Micelles; D011137:Polystyrenes; D011145:Polyvinyls; C522357:poly(N-vinyl-pyrrolidone)-block-poly(D,L-lactide); D014867:Water; D015742:Propofol