乙醇对氯胺酮在家兔体内毒物代谢动力学的影响研究

发布时间：2018-01-24 08:40

本文关键词： 法医毒物学氯胺酮乙醇毒物代谢动力学家兔显著性差异动力学参数代谢物合用动力学过程　出处：《中国法医学杂志》2010年01期 　论文类型：期刊论文

【摘要】：目的研究乙醇对氯胺酮在家兔体内毒物代谢动力学行为的影响。方法实验家兔分为单用氯胺酮组、氯胺酮与乙醇合用组及对照组,三组动物分别灌胃氯胺酮0.15 g/kg、乙醇3.0g/kg与氯胺酮0.15 g/kg及等体积生理盐水。分别于给药前和给药后不同时间点收集血、尿标本,GC和GC/MS法测定氯胺酮和代谢物去甲氯胺酮浓度,WinNor-Lin软件拟合房室模型并计算氯胺酮和去甲氯胺酮毒物代谢动力学参数。结果氯胺酮在家兔体内的毒物代谢动力学过程呈一级动力学特征,符合二室开放模型,合用乙醇后不改变其房室类型。合用乙醇组家兔体内氯胺酮的K10、AUC和β均大于单用氯胺酮组,而T1/2K10、T1/2β、A和Cmax均小于单用氯胺酮组,两组之间存在显著性差异(P0.05);V/F、K01、K12、K21、T1/2K01、α、T1/2α、Tmax和B等参数两组之间无显著性差异(P0.05)。合用乙醇组家兔体内氯胺酮的代谢物去甲氯胺酮的K01、A、B和Cmax等参数均大于单用氯胺酮组,而T1/2K01、Tmax均小于单用氯胺酮组,两组之间存在显著性差异(P0.05);V/F、K10、K12、K21、AUC、T1/2K10、T1/2α、T1/2β、β等参数两组之间无显著性差异(P0.05)。结论乙醇可加快氯胺酮在体内的消除过程,促进其转化为去甲氯胺酮,对于氯胺酮与乙醇合并滥用的鉴定,应考虑两者的相互作用。
[Abstract]:Objective to study the effect of ethanol on the metabolic behavior of ketamine in rabbits. Methods Rabbits were divided into single ketamine group, ketamine combined with ethanol group and control group. Ketamine 0.15 g / kg was administered intragastrically in the three groups. Ethanol 3.0 g / kg, ketamine 0.15 g / kg and saline of the same volume. Blood and urine samples were collected at different time points before and after administration. The concentrations of ketamine and norketamine were determined by GC and GC/MS. WinNor-Lin software fitted the atrioventricular model and calculated the pharmacokinetic parameters of ketamine and norketamine. Results Ketamine metabolism in rabbits showed first-order kinetic characteristics. The K10 AUC and 尾 of ketamine group were higher than that of ketamine alone group, but T1 / 2K10 T1 / 2 尾. Both A and Cmax were lower than those in ketamine group, and there was a significant difference between the two groups (P 0.05). V / F FK01N K12K21 T1 / 2K01a T1 / 2K01a T1 / 2 伪. There was no significant difference between the two groups in Tmax and B parameters. K01A of norketamine was the metabolite of ketamine in combination with ethanol group. The parameters of B and Cmax were higher than those of ketamine group, while T1 / 2K01Tmax was lower than that of Ketamine group, there was significant difference between the two groups (P0.05). V / F K10 K12 K21 AUC T1 / 2K10 T1 / 2 伪 T1 / 2 尾. Conclusion ethanol can accelerate the elimination process of ketamine in vivo and promote its transformation into norketamine, and identify the combined abuse of ketamine and ethanol. The interaction between the two should be considered.
【作者单位】：山西医科大学法医学院;
【基金】：“十一五”国家科技支撑计划项目基金(2007BAK26B05) 山西省自然科学基金资助项目(2007011105) 山西高校科技研究开发项目(20041319)
【分类号】：D919.1
【正文快照】： 氯胺酮(ketamine,简称KE)属N-甲基-D-天门冬氨酸(NMDA)受体拮抗剂,同属NMDA受体拮抗剂的还有乙醇和PCP等[1]。氯胺酮入体后70%~90%经肝P450酶主要代谢为去甲氯胺酮(norketamine,简称NK)。氯胺酮是一种麻醉药,也是一种滥用药,具有一定的精神依赖性[2]。在氯胺酮滥用人员中多种

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