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高原环境对大鼠丙泊酚药代动力学的影响。

Altitude effect on Propofol Pharmacokinetics in Rats.

机构信息

Department of Anesthesiology, The First People's Hospital of Ziyang City, Ziyang 641300, China.

Department of Anesthesiology, Qinghai Red Cross Hospital, Xining 810000, China.

出版信息

Curr Drug Metab. 2024;25(1):81-90. doi: 10.2174/0113892002285571240220131547.

DOI:10.2174/0113892002285571240220131547
PMID:38468514
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11327735/
Abstract

BACKGROUND

Propofol is an intravenous agent for clinical anesthesia. As the influence of the hypobaric-hypoxic environment (Qinghai-Tibetan region, altitude: 2800-4300 m, PaO2: 15.1-12.4 kPa) on the metabolism of Propofol is complex, the research results on the metabolic characteristics of Propofol in high-altitude areas remain unclear. This study aimed to investigate the pharmacokinetic characteristics of Propofol in a high-altitude hypoxic environment using animal experiments.

METHODS

Rats were randomly divided into three groups: high-altitude, medium-altitude, and plain groups. The time of disappearance and recovery of the rat righting reflex was recorded as the time of anesthesia induction and awakening, respectively. The plasma concentration of Propofol was determined by gas chromatography-mass spectrometry. A pharmacokinetic analysis software was used to analyze the blood-drug concentrations and obtain the pharmacokinetic parameters.

RESULTS

We observed that when Propofol anesthetizes rats, the anesthesia induction time was shortened, and the recovery time was prolonged with increased altitude. Compared with the plain group, the clearance of Propofol decreased, whereas the half-life, area under the concentration-time curve, peak plasma concentration, and average residence time extension increased.

CONCLUSION

The pharmacokinetic characteristics of Propofol are significantly altered in high-altitude hypoxic environments.

摘要

背景

丙泊酚是一种临床麻醉用的静脉内给药制剂。由于低压低氧环境（青海-西藏地区，海拔：2800-4300 米，PaO2：15.1-12.4kPa）对丙泊酚代谢的影响较为复杂，关于丙泊酚在高原地区代谢特征的研究结果尚不清楚。本研究旨在通过动物实验探讨高原缺氧环境下丙泊酚的药代动力学特征。

方法

将大鼠随机分为三组：高原组、中海拔组和平原组。记录大鼠翻正反射消失和恢复的时间作为麻醉诱导和苏醒的时间。采用气相色谱-质谱法测定丙泊酚的血浆浓度。使用药代动力学分析软件分析血药浓度，得出药代动力学参数。

结果

我们观察到，当丙泊酚麻醉大鼠时，随着海拔的升高，麻醉诱导时间缩短，苏醒时间延长。与平原组相比，丙泊酚的清除率降低，半衰期、浓度-时间曲线下面积、血浆峰浓度和平均停留时间延长。

结论

高原缺氧环境会显著改变丙泊酚的药代动力学特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b595/11327735/57338679f333/CDM-25-81_F10.jpg
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本文引用的文献

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The Influences and Mechanisms of High-altitude Hypoxia Exposure on Drug Metabolism.高原缺氧暴露对药物代谢的影响及其机制。
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Dopamine transporter in the ventral tegmental area modulates recovery from propofol anesthesia in rats.腹侧被盖区的多巴胺转运体调节大鼠丙泊酚麻醉后的恢复。
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Exposure to High-Altitude Environment Is Associated with Drug Transporters Change: microRNA-873-5p-Mediated Alteration of Function and Expression Levels of Drug Transporters under Hypoxia.暴露于高海拔环境与药物转运体的变化有关：低氧下 microRNA-873-5p 介导的药物转运体功能和表达水平的改变。
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Pharmacokinetics of Acetaminophen and Metformin Hydrochloride in Rats After Exposure to Simulated High Altitude Hypoxia.大鼠暴露于模拟高海拔低氧环境后对乙酰氨基酚和盐酸二甲双胍的药代动力学研究
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