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体外膜肺氧合对盐酸右美托咪定药代动力学的影响

The Effect of Extracorporeal Membrane Oxygenation on the Pharmacokinetics of Dexmedetomidine Hydrochloride.

作者信息

Wang Tao, Zhang Huifang, Tian Rui, Rong Liu, Yang Kaige, Wang Yan, Wang Ruilan

机构信息

Department of Critical Care Medicine, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, China; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200080, China.

Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200080, China.

出版信息

J Cardiothorac Vasc Anesth. 2025 Mar;39(3):616-624. doi: 10.1053/j.jvca.2024.12.029. Epub 2024 Dec 18.

Abstract

OBJECTIVES

Our objective was to explore the effects of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics of dexmedetomidine hydrochloride via vitro and in vivo experiments DESIGN: A single-center animal investigation.

SETTING

An experimental animal facility in a tertiary hospital.

PARTICIPANTS

Eighteen male Landrace pigs.

INTERVENTIONS

For the in vitro experiment, ECMO circuits were primed with whole blood solutions of dexmedetomidine at different concentrations and ran ex vivo. The adsorption rates of dexmedetomidine hydrochloride in ECMO circuits and control glass tubes were compared at 60 minutes, 5 hours, and 10 hours after the start of the in vitro experiment. In the in vivo experiment, 12 Landrace pigs were randomly allocated to the venovenous ECMO group or the control group. Dexmedetomidine hydrochloride (1 μg/kg) was administered to both groups. Blood samples were collected at 0 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 2 hours, 3 hours, 5 hours, 7 hours, and 10 hours after administration. The plasma concentrations of dexmedetomidine were measured, and pharmacokinetic analysis was conducted in both groups.

MEASUREMENTS AND MAIN RESULTS

The results revealed no significant difference in adsorption rates of dexmedetomidine hydrochloride in ECMO circuits at 60 minutes and 5 hours, but differences were observed at 10 hours. In vivo experiment, pharmacokinetic analysis revealed no significant difference in the area under the curve (AUC), AUC, distribution half-life, elimination half-life, clearance, apparent volume of distribution, mean residence time or peak drug concentrations between the 2 groups (p > 0.05).

CONCLUSIONS

The ECMO circuit had an adsorption effect on dexmedetomidine hydrochloride, but this effect was not sufficient to impact the in vivo pharmacokinetics of dexmedetomidine significantly. The effect of ECMO on the pharmacokinetics of dexmedetomidine hydrochloride was not significant.

摘要

目的

我们的目的是通过体外和体内实验探索体外膜肺氧合(ECMO)对盐酸右美托咪定药代动力学的影响。

设计

单中心动物研究。

地点

一家三级医院的实验动物设施。

参与者

18只雄性长白猪。

干预措施

在体外实验中,用不同浓度的盐酸右美托咪定全血溶液预充ECMO回路,并进行体外运行。在体外实验开始后60分钟、5小时和10小时,比较盐酸右美托咪定在ECMO回路和对照玻璃管中的吸附率。在体内实验中,将12只长白猪随机分配到静脉-静脉ECMO组或对照组。两组均给予盐酸右美托咪定(1μg/kg)。给药后0分钟、5分钟、10分钟、15分钟、20分钟、30分钟、45分钟、60分钟、90分钟、2小时、3小时、5小时、7小时和10小时采集血样。测定两组血浆中盐酸右美托咪定的浓度,并进行药代动力学分析。

测量指标和主要结果

结果显示,在60分钟和5小时时,盐酸右美托咪定在ECMO回路中的吸附率无显著差异,但在10小时时观察到差异。在体内实验中,药代动力学分析显示两组之间的曲线下面积(AUC)、AUC、分布半衰期、消除半衰期、清除率、表观分布容积、平均驻留时间或药物峰值浓度无显著差异(p>0.05)。

结论

ECMO回路对盐酸右美托咪定有吸附作用,但这种作用不足以显著影响盐酸右美托咪定的体内药代动力学。ECMO对盐酸右美托咪定药代动力学的影响不显著。

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