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 ml21) 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, Diprivanw to male Sprague–Dawley rats (n 40) at a dose of 10 mg kg21. 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 formu-lation (Diprivanw or Propofol-PM) as covariates. Sample matrix was applied to all structural model parameters as a dichotomous covariate. An influence of propofol formulation wa