Altitude effect on Propofol Pharmacokinetics in Rats.

IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current drug metabolism Pub Date : 2024-01-01 DOI:10.2174/0113892002285571240220131547
Lijun Li, Xuejun Wang, Sheng Wang, Li Wen, Haopeng Zhang
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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.

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海拔高度对大鼠丙泊酚药代动力学的影响
背景介绍丙泊酚是一种用于临床麻醉的静脉注射剂。由于低压缺氧环境(青藏地区,海拔:2800-4300 m,PaO2:15.1-12.4 kPa)对丙泊酚代谢的影响较为复杂,有关丙泊酚在高海拔地区代谢特征的研究结果尚不明确。本研究旨在通过动物实验研究丙泊酚在高海拔缺氧环境下的药代动力学特征:方法:将大鼠随机分为三组:高海拔组、中海拔组和普通组。大鼠右反射消失和恢复的时间分别记录为麻醉诱导时间和苏醒时间。采用气相色谱-质谱法测定血浆中丙泊酚的浓度。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:丙泊酚麻醉大鼠时,随着海拔的升高,麻醉诱导时间缩短,恢复时间延长。与普通组相比,丙泊酚的清除率降低,而半衰期、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:在高海拔缺氧环境中,丙泊酚的药代动力学特征会发生显著变化。
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来源期刊
Current drug metabolism
Current drug metabolism 医学-生化与分子生物学
CiteScore
4.30
自引率
4.30%
发文量
81
审稿时长
4-8 weeks
期刊介绍: Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.
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