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丙泊酚在体外临床靶血浆浓度下不改变利多卡因的蛋白结合和未结合浓度-一个简短的交流。

Propofol does not alter the protein binding and unbound concentration of lidocaine at clinically targeted plasma concentrations in vitro - A short communication.

机构信息

Department of Anaesthesia and Perioperative Medicine, The Royal Brisbane and Women's Hospital, Butterfield St, Herston 4006, Queensland, Australia; Faculty of Medicine, The University of Queensland, St Lucia 4067, Queensland, Australia.

The University of Queensland Centre for Clinical Research, The University of Queensland, Herston 4006, Queensland, Australia; Departments of Pharmacy and Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Butterfield St, Herston 4006, Queensland, Australia; Herston Infectious Diseases Institute (HeIDI), Metro North Health, Herston 4006, Queensland, Australia; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.

出版信息

Anaesth Crit Care Pain Med. 2024 Oct;43(5):101419. doi: 10.1016/j.accpm.2024.101419. Epub 2024 Jul 30.

Abstract

BACKGROUND

Intravenous lidocaine is increasingly used as an analgesic adjunct during general anaesthesia. Lidocaine is highly protein-bound and changes to binding can alter drug efficacy or toxicity. We aimed to measure the effect of various propofol and lidocaine plasma concentration combinations on the protein binding and concentration of lidocaine in vitro.

METHODS

Known targeted concentrations of propofol and lidocaine were added to drug-free human plasma in vitro. Samples were prepared and analysed in various clinically relevant concentration combinations; propofol at 0, 2, 4 and 6 µg/mL, and lidocaine at 1, 3 and 5 µg/mL. The total and unbound concentrations of lidocaine were measured by ultra-high performance liquid chromatography-mass spectrometry and percentage protein binding was determined. Data were presented as mean and standard deviation (SD) and differences between groups analysed.

RESULTS

The overall mean protein binding of lidocaine was 68.8% (SD 5.5, range 57.5-80.9%). Beta regression analysis revealed no statistically significant difference in lidocaine percentage binding across a range of propofol and lidocaine concentration combinations.

CONCLUSION

Propofol did not alter the unbound and free pharmacologically active proportion of lidocaine at different clinically targeted concentrations of propofol and lidocaine in plasma in vitro. The percentage of plasma protein binding of lidocaine in this study was consistent with previously published results.

摘要

背景

静脉注射利多卡因在全身麻醉中越来越多地被用作辅助镇痛剂。利多卡因高度结合蛋白,结合的变化可能改变药物的疗效或毒性。我们旨在测量各种丙泊酚和利多卡因血浆浓度组合对体外利多卡因蛋白结合和浓度的影响。

方法

在体外向无药物的人血浆中加入已知目标浓度的丙泊酚和利多卡因。以各种临床相关的浓度组合(丙泊酚 0、2、4 和 6μg/mL,利多卡因 1、3 和 5μg/mL)制备和分析样品。通过超高效液相色谱-质谱法测量利多卡因的总浓度和未结合浓度,并确定蛋白结合百分比。数据以平均值和标准差(SD)表示,并对组间差异进行分析。

结果

利多卡因的总体平均蛋白结合率为 68.8%(SD 5.5,范围 57.5-80.9%)。贝塔回归分析显示,在不同的丙泊酚和利多卡因浓度组合范围内,利多卡因的结合百分比没有统计学上的显著差异。

结论

在体外不同临床靶向浓度的丙泊酚和利多卡因血浆中,丙泊酚并未改变利多卡因的未结合和游离药理学活性比例。本研究中利多卡因的血浆蛋白结合百分比与先前发表的结果一致。

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