Ward Denham S, Norton J Russell, Guivarc'h Pol-Henri, Litman Ronald S, Bailey Peter L
Department of Anesthesiology, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 604, Rochester, NY 14642, USA.
Anesthesiology. 2002 Dec;97(6):1401-8. doi: 10.1097/00000542-200212000-00011.
Because propofol is water insoluble, current formulations of propofol use a soybean oil emulsion. These soybean emulsions cause elevated plasma triglycerides and support bacterial growth. This study compares an alternative formulation of propofol as a 2% emulsion in a medium-chain triglyceride solution (IDD-D Propofol) with Diprivan.
This double-blind, crossover, phase 1 study compared IDD-D Propofol with Diprivan using two consecutive protocols of 12 subjects each. Subjects in protocol 1 received a single bolus of 2.5 mg/kg, and those in protocol 2 received the same induction dose followed by a 30-min infusion at 0.2 mg. kg(-1).min(-1). Venous samples were taken for propofol concentration and biochemical measurements. Induction and emergence times were measured by termination of voluntary counting and responding to command, respectively.
Plasma concentrations were not different between the two formulations. Induction time was 14% longer with IDD-D Propofol than with Diprivan (N = 24, protocols 1 and 2 combined, 53.3 +/- 12.1 s and 46.9 +/- 7.8 s, respectively; P = 0.002). Emergence time was not significantly different for protocol 1 but was marginally longer (P = 0.04) for IDD-D Propofol in protocol 2 (1,197 +/- 445 s [n = 11] and 1,254 +/- 468 s [n = 12], respectively). As expected because of the inherent characteristics of the formulations, plasma triglycerides were elevated for Diprivan but not for IDD-D Propofol; octanoate, a metabolite of medium-chain triglycerides, was elevated only with IDD-D Propofol. Octanoate was elevated to concentrations below those considered toxic. Plasma concentrations of other biochemical markers of medium-chain triglyceride metabolism, ketones, showed no significant changes. Interestingly, there were significant differences between male and female subjects in the propofol plasma concentrations and time to awakening with both drugs.
Differences between the two propofol formulations were slight and not clinically significant. Similar gender differences in plasma concentrations and awaking times were found for both formulations.
由于丙泊酚不溶于水，目前丙泊酚制剂使用大豆油乳剂。这些大豆乳剂会导致血浆甘油三酯升高并有利于细菌生长。本研究比较了丙泊酚的一种替代制剂，即中链甘油三酯溶液中的2%乳剂（IDD-D丙泊酚）与得普利麻。
这项双盲、交叉的1期研究使用两个连续的方案，每个方案有12名受试者，对IDD-D丙泊酚和得普利麻进行比较。方案1中的受试者接受2.5mg/kg的单次推注，方案2中的受试者接受相同的诱导剂量，随后以0.2mg·kg⁻¹·min⁻¹的速度输注30分钟。采集静脉血样用于测定丙泊酚浓度和生化指标。诱导时间和苏醒时间分别通过终止自主计数和对指令做出反应来测量。
两种制剂的血浆浓度无差异。IDD-D丙泊酚的诱导时间比得普利麻长14%（N = 24，方案1和方案2合并，分别为53.3±12.1秒和46.9±7.8秒；P = 0.002）。方案1中，两种制剂的苏醒时间无显著差异，但方案2中IDD-D丙泊酚的苏醒时间略长（P = 0.04）（分别为1197±445秒[n = 11]和1254±468秒[n = 12]）。由于制剂的固有特性，正如预期的那样，得普利麻组的血浆甘油三酯升高，而IDD-D丙泊酚组未升高；辛酸是中链甘油三酯的代谢产物，仅在IDD-D丙泊酚组中升高。辛酸升高至低于有毒浓度。中链甘油三酯代谢的其他生化标志物（酮体）的血浆浓度无显著变化。有趣的是，两种药物在丙泊酚血浆浓度和苏醒时间方面，男性和女性受试者之间存在显著差异。
两种丙泊酚制剂之间的差异很小，无临床意义。两种制剂在血浆浓度和苏醒时间方面均发现了类似的性别差异。
