University of Groningen, University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands.
University of Groningen, University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands.
Br J Anaesth. 2018 Jun;120(6):1401-1411. doi: 10.1016/j.bja.2018.01.038. Epub 2018 Mar 28.
Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers.
Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg min or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring.
No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift.
Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern.
NTR4735.
环丙基甲氧羰基甲灭酸，或 ABP-700，是依托咪酯的第二代类似物，旨在保留依托咪酯有益的血液动力学和呼吸模式，同时减少其对肾上腺皮质轴的抑制。本研究的目的是描述 ABP-700 30 分钟持续输注的安全性和疗效，并评估其对健康人体志愿者的血液动力学和肾上腺皮质反应的影响。
五个队列共 40 名受试者接受递增剂量的 ABP-700、丙泊酚 60μg/kg/min 或安慰剂输注。通过不良事件（AE）监测、安全实验室检查和动脉血气来评估安全性。通过连续监测评估血液动力学和呼吸稳定性。通过促肾上腺皮质激素（ACTH）刺激试验分析肾上腺皮质功能。使用改良观察者评估警觉/镇静（MOAA/S）和连续双谱指数监测来测量临床效果。
未报告严重 AE。血液动力学和呼吸效应包括轻度剂量依赖性心动过速、血压略有升高，以及无中枢介导的呼吸暂停。在 ACTH 刺激下，未观察到任何受试者的肾上腺皮质抑制。报告了不自主肌肉运动（IMM），随着剂量方案的增加，IMM 更为广泛。ABP-700 较高剂量与更深的镇静和更高的镇静可能性相关。临床效果的起始时间在各个队列中各不相同，恢复迅速。
ABP-700 输注表现出剂量依赖性催眠作用，不会引起严重低血压、严重呼吸抑制或肾上腺皮质抑制。不自主肌肉运动的出现和性质令人关注。
NTR4735。
