Isobolographic analysis of propofol-thiopental hypnotic interaction in surgical patients.
Isobolographic analysis of propofol-thiopental hypnotic interaction in surgical patients.
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手术患者异丙酚-硫喷妥钠催眠相互作用的等辐射线分析。
DOI：
10.1097/00000539-199903000-00037
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发表时间：
1999
影响因子：
5.7
通讯作者：
Kissin,I
中科院分区：
文献类型：
--
作者：
Vinik,HR;BradleyJr,EL;Kissin,I
通过相同机制作用的药物相互作用是相加的，而超相加效应可能是具有不同作用机制的药物相互作用的结果。咪达唑仑-异丙酚和咪达唑仑-硫喷妥钠的相互作用是超加性的。与咪达唑仑相比，异丙酚和硫喷妥钠的作用机制非常相似。本研究的目的是验证这一假说，即异丙酚和硫喷妥钠作用机制的相似性导致了加性催眠相互作用。我们以随机、双盲的方式研究了硫喷妥钠、异丙酚及其联合用药对150名未用药患者的催眠作用。根据命令睁开眼睛的能力被用作终点。用概率法测定单独给药和联合给药在3种不同剂量比下的剂量-反应曲线，并用等谱分析和代数(分数)分析比较50%有效剂量值。催眠药异丙酚和硫喷妥钠的组份之间的所有剂量比都是相加的。咪达唑仑-硫喷妥钠或异丙酚-咪达唑仑联合用药缺乏异丙酚-硫喷妥钠的协同作用，这表明异丙酚和硫喷妥钠的催眠作用机制与上述咪达唑仑联合用药非常相似，可能是相同的。异丙酚和硫喷妥钠的催眠作用是相加的。
Drugs acting via the same mechanism interact additively, whereas a supraadditive effect can result from an interaction of drugs with different mechanisms of action. Hypnotic midazolam-propofol and midazolam-thiopental interactions are supraadditive. In contrast to midazolam, the mechanisms of actions of propofol and thiopental are quite similar. The aim of this study was to test the hypothesis that similarity in the mechanisms of action of propofol and thiopental results in the additive hypnotic interaction. We studied the hypnotic effects of thiopental, propofol, and their combinations in 150 unpremedicated patients in a randomized, double-blind fashion. The ability to open eyes on command was used as an end point. Dose-response curves for the drugs given separately and in combinations at three different dose ratios between the drugs were determined by using a probit procedure, and the 50% effective dose values were compared by using isobolographic and algebraic (fractional) analysis. The hypnotic propofol-thiopental combination was additive with all dose ratios between components of the combination. The absence of propofol-thiopental synergy, as demonstrated with midazolam-thiopental or propofol-midazolam combinations, suggests that the mechanisms underlying the hypnotic effects of propofol and thiopental, in contrast to the above combinations with midazolam, are very similar and could be identical. Implications: The propofol-thiopental hypnotic interaction is additive.