Egan Talmage D, Kern Steven E, Johnson Kenward B, Pace Nathan L
Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City, USA.
Anesth Analg. 2003 Jul;97(1):72-9, table of contents. doi: 10.1213/01.ane.0000066019.42467.7a.
The currently marketed propofol formulation has a number of undesirable properties that are in part a function of the lipid emulsion formulation, including pain on injection, serious allergic reactions, and the support of microbial growth. A modified cyclodextrin-based formulation of propofol (sulfobutyl ether-beta-cyclodextrin) has been developed that may mitigate some of these formulation-dependent problems. However, reformulation may alter propofol's pharmacologic behavior. Our aim in this study was to compare the pharmacokinetics and pharmacodynamics of propofol in the currently marketed lipid-based formulation with those of the novel cyclodextrin formulation. We hypothesized that the pharmacokinetics and pharmacodynamics of the propofol in cyclodextrin would be substantially similar to those of the propofol in lipid. Thirty-two isoflurane-anesthetized animals were instrumented with pulmonary artery, arterial, and IV catheters and were randomly assigned to receive either propofol in lipid or propofol in cyclodextrin by continuous infusion. Arterial blood samples for propofol assay were collected. The processed electroencephalogram, heart rate, mean arterial blood pressure, and cardiac output were measured continuously. The propofol formulations were compared by using model-independent analysis techniques. Combined kinetic/dynamic models were also constructed for simulation purposes. There were no significant differences in the pharmacokinetics or pharmacodynamics of the two propofol formulations. The simulations based on the combined pharmacokinetic/pharmacodynamic models confirmed the substantial similarity of the two formulations. The hypothesis that the propofol-in-cyclodextrin formulation would exhibit pharmacokinetic and pharmacodynamic behavior that was substantially similar to the propofol-in-lipid formulation was confirmed.
A modified cyclodextrin-based formulation of propofol has been developed that may mitigate some of the problems associated with propofol in lipid emulsion. However, reformulation of propofol may change its clinical characteristics. This study in a pig model showed that the novel propofol formulation was substantially similar to the lipid emulsion propofol formulation.
目前市售的丙泊酚制剂有许多不良特性，部分是脂质乳剂制剂的作用，包括注射疼痛、严重过敏反应以及支持微生物生长。已开发出一种基于环糊精的丙泊酚改良制剂（磺丁基醚-β-环糊精），可能会减轻其中一些与制剂相关的问题。然而，重新配方可能会改变丙泊酚的药理行为。我们在本研究中的目的是比较市售脂质基制剂中的丙泊酚与新型环糊精制剂的丙泊酚的药代动力学和药效学。我们假设环糊精中丙泊酚的药代动力学和药效学与脂质中丙泊酚的药代动力学和药效学基本相似。32只异氟烷麻醉的动物通过肺动脉、动脉和静脉导管进行监测，并随机分配通过持续输注接受脂质中的丙泊酚或环糊精中的丙泊酚。采集动脉血样本用于丙泊酚测定。连续测量处理后的脑电图、心率、平均动脉血压和心输出量。使用非模型分析技术比较丙泊酚制剂。还构建了联合动力学/动力学模型用于模拟目的。两种丙泊酚制剂的药代动力学或药效学没有显著差异。基于联合药代动力学/药效学模型的模拟证实了两种制剂的基本相似性。环糊精中丙泊酚制剂将表现出与脂质中丙泊酚制剂基本相似的药代动力学和药效学行为这一假设得到了证实。
已开发出一种基于环糊精的丙泊酚改良制剂，可能会减轻与脂质乳剂中丙泊酚相关的一些问题。然而，丙泊酚的重新配方可能会改变其临床特性。这项在猪模型中的研究表明，新型丙泊酚制剂与脂质乳剂丙泊酚制剂基本相似。
