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吗啡灌注兔:法医昆虫毒理学实验的一种工具。

Morphine perfused rabbits: a tool for experiments in forensic entomotoxicology.

作者信息

Hédouin V, Bourel B, Martin-Bouyer L, Bécart A, Tournel G, Deveaux M, Gosset D

机构信息

Institut de Médecine Légale et de Médecine Sociale, Lille, France.

出版信息

J Forensic Sci. 1999 Mar;44(2):347-50.

Abstract

In order to establish an animal model for entomotoxicological studies, the kinetics of morphine elimination from blood after a single intravenous injection of morphine and the concentration of morphine in tissues following a continuous perfusion were studied. The aim of these experiments was to obtain controlled morphine tissue concentrations similar to those encountered in fatal human heroin overdoses. These tissues can be used as a food source for developing fly larvae in entomotoxicological studies. In the single injection experiment, seven rabbits were administered 1 or 2 mg/kg body weight of morphine chlorhydrate via the main ear artery. Blood samples of 200 microL were removed regularly via a catheter. Morphine concentration was determined using RIA techniques. Morphine was found to be first rapidly distributed and then slowly eliminated, following a two-exponential equation. Elimination of morphine from blood can be described as a two-compartment model. Constants of the equation were determined using the Kaleidagraph program. Using those constants, the main pharmacokinetics parameters were calculated. Results of these parameters showed the following: clearance from 13.3 to 16.2 L.h.1, half-life of the distribution phase from 0.6 to 0.9 min, and half-life of the elimination phase from 21 to 26 min. These results were used to calculate the rate of perfusion of morphine for rabbits to obtain desired, controlled, and constant concentrations of morphine in tissues. In the second experiment, three rabbits received a perfusion of morphine intravascularly at a rate of 2 mg/kg/h for a period of 3 h. These rabbits were sacrificed and analyses performed on several abdominal and thoracic organs. Results showed that the concentrations of morphine differed according to the organ analyzed, but were reproducible for organs between animals. These concentrations were similar to those normally encountered in cases of human death due to heroin overdoses.

摘要

为建立昆虫毒理学研究的动物模型,研究了单次静脉注射吗啡后吗啡从血液中消除的动力学以及连续灌注后组织中吗啡的浓度。这些实验的目的是获得与人类致命海洛因过量中毒时相似的可控吗啡组织浓度。在昆虫毒理学研究中,这些组织可作为发育蝇幼虫的食物来源。在单次注射实验中,通过主耳动脉给7只兔子注射1或2mg/kg体重的盐酸吗啡。通过导管定期采集200μL血样。使用放射免疫分析技术测定吗啡浓度。发现吗啡首先快速分布,然后缓慢消除,符合双指数方程。吗啡从血液中的消除可描述为二室模型。使用Kaleidagraph程序确定方程的常数。利用这些常数计算主要药代动力学参数。这些参数的结果如下:清除率为13.3至16.2L·h⁻¹,分布相半衰期为0.6至0.9分钟,消除相半衰期为21至26分钟。这些结果用于计算兔子吗啡灌注速率,以在组织中获得所需的、可控的和恒定的吗啡浓度。在第二个实验中,3只兔子以2mg/kg/h的速率进行3小时的血管内吗啡灌注。处死这些兔子并对几个腹部和胸部器官进行分析。结果表明,吗啡浓度因分析的器官而异,但在不同动物的相同器官之间具有可重复性。这些浓度与人类海洛因过量致死病例中通常遇到的浓度相似。

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