Ravenelle F, Vachon P, Rigby-Jones A E, Sneyd J R, Le Garrec D, Gori S, Lessard D, Smith D C
Labopharm Inc., 480 Blvd. Armand-Frappier, Laval, Québec, Canada H7V 4B4.
Br J Anaesth. 2008 Aug;101(2):186-93. doi: 10.1093/bja/aen147. Epub 2008 Jun 11.
As a result of its very low water solubility, propofol is generally presented as a lipid-based formulation with well-characterized limitations.
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.
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.
Propofol-PM formulations produce anaesthesia in rats. Whole blood pharmacokinetics of Propofol-PM did not differ from those observed with Diprivan.
由于丙泊酚的水溶性极低，其通常以具有明确局限性的脂质制剂形式呈现。
将丙泊酚（99.7%）直接加入聚（N-乙烯基-2-吡咯烷酮）-嵌段-聚（D，L-丙交酯）共聚物（PVP-PLA）嵌段共聚物的水溶液中并搅拌，以获得澄清溶液。该制剂经无菌过滤后冻干成固体形式的丙泊酚-PM（丙泊酚聚合物胶束），其重构为含30 - 60纳米丙泊酚胶束的1%w/v（10毫克/毫升）澄清丙泊酚水溶液。通过给雄性Sprague-Dawley大鼠（n = 40）以10毫克/千克的剂量给予重构的丙泊酚-PM制剂和1%水包油制剂得普利麻，获得全血和血浆的群体药代动力学数据。从另一项小型研究中获得初步恢复数据。
药代动力学用两室乳突状群体模型能得到最佳描述，该模型将样本基质（血液或血浆）和丙泊酚制剂（得普利麻）或丙泊酚-PM作为协变量。样本基质作为二分协变量应用于所有结构模型参数。观察到丙泊酚制剂对所有参数（不包括分布清除率）有影响，但仅在使用血浆进行丙泊酚定量时。在这项初步药效学研究中，丙泊酚-PM制剂组和得普利麻组之间恢复终点的时间没有统计学上的显著差异。
丙泊酚-PM制剂在大鼠中产生麻醉作用。丙泊酚-PM的全血药代动力学与得普利麻观察到的药代动力学没有差异。
