Schüttler J, Schwilden H, Stoeckel H
Eur J Anaesthesiol. 1985 Jun;2(2):133-42.
Etomidate was administered to six healthy volunteers by microprocessor controlled infusions, to generate three cycles of linearly increasing plasma levels, with an anticipated slope of 0.05 microgram ml-1 min-1. The infusions were stopped when a deep hypnotic state was obtained, as indicated by burst suppressions in the EEG. The infusions were restarted when the volunteers were fully orientated to person, place and time. The mean (+/-SD) doses of etomidate delivered by the first, second and third infusion were 165 +/- 30, 137 +/- 25 and 157 +/- 26 mg, respectively. Certain clinical signs were observed and related to the plasma concentrations of etomidate. Pharmacokinetic analysis was undertaken using an open two-compartment model. The therapeutic window was in a range of plasma concentrations between 0.3 and 1.0 microgram ml-1 of etomidate. Pharmacokinetic analysis gave a volume for the central compartment of 50 +/- 11 litre, an apparent volume of distribution of 252 +/- 51 litre and a total clearance of 1693 +/- 504 ml min-1. Microprocessor controlled infusions can serve as a powerful tool for research in clinical pharmacology. The achievement of linearly increasing plasma levels of etomidate allowed further pharmacokinetic and pharmacodynamic modelling concepts to be realized.
依托咪酯通过微处理器控制输注给予6名健康志愿者，以产生三个血浆水平呈线性增加的周期，预期斜率为0.05微克/毫升·分钟。当脑电图出现爆发抑制，表明达到深度催眠状态时，停止输注。当志愿者对人物、地点和时间完全定向时，重新开始输注。第一次、第二次和第三次输注给予的依托咪酯平均（±标准差）剂量分别为165±30、137±25和157±26毫克。观察到某些临床体征并与依托咪酯的血浆浓度相关。使用开放二室模型进行药代动力学分析。治疗窗处于依托咪酯血浆浓度0.3至1.0微克/毫升的范围内。药代动力学分析得出中央室容积为50±11升，表观分布容积为252±51升，总清除率为1693±504毫升/分钟。微处理器控制输注可作为临床药理学研究的有力工具。依托咪酯血浆水平呈线性增加，使得进一步的药代动力学和药效学建模概念得以实现。
