氯胺酮在家兔体内的毒物代谢动力学  

Toxicokinetics of Ketamine in Rabbits

作　　者：刘玲[1] 尉志文[1] 贾娟[1] 王玉瑾[1] 

机构地区：[1]山西医科大学法医学院,山西太原030001

出　　处：《法医学杂志》2010年第5期357-360,共4页Journal of Forensic Medicine

基　　金：山西省自然科学基金资助项目(2007011105);"十一五"国家科技支撑计划项目(2007BAK26B05);山西高校科技研究开发项目(20041319)

摘　　要：目的研究氯胺酮及其代谢物去甲氯胺酮在家兔体内的毒物代谢动力学特征。方法家兔以氯胺酮0.15g/kg剂量灌胃,分别于给药前和给药后不同时间点收集血液和尿液,血清和尿液中氯胺酮及代谢物用GC-MS法定性、GC-NPD法定量检测,WinNorLin软件拟合房室模型并计算毒物代谢动力学参数。全程记录实验动物主要生命体征变化。结果氯胺酮和代谢物去甲氯胺酮在家兔体内的毒物代谢动力学过程均呈一级动力学特征,符合二室开放模型,氯胺酮毒物代谢动力学方程为ρt=121.760e-0.025t+0.980e-0.002t+4.579 e-0.021t,去甲氯胺酮毒物代谢动力学方程为ρt=640.919 e-0.03t+1.023 e-0.001t+9.784 e-0.031t。血液中氯胺酮质量浓度达峰时间为(40.950±12.098)min,血峰质量浓度为(9.015±1.344)μg/mL,消除半衰期为(430.370±28.436)min。给药后30～240 min内氯胺酮在血清和尿液中的质量浓度之间具有动态平衡的中度相关性。家兔给药后30min出现中毒症状,120min后渐恢复正常。结论建立的氯胺酮毒物代谢动力学方程和参数可为氯胺酮分析的合理取样、从血药质量浓度推断服药时间以及氯胺酮滥用的法医学鉴定提供理论依据。Objective To investigate the toxicokinetics profiles of ketamine and its main metabolite norketamine in rabbits.Methods The rabbits were administered orally the hydrochloride of ketamine with a dose of 0.15 g/kg.The serum and urine samples were collected before administration and at different time points after drug administration.The concentrations of ketamine and norketamine were determined by GC-NPD and GC-MS.Compartment model and toxicokinetics parameters were simulated and calculated by WinNor-Lin program.Changes of important vital signs of rabbits were recorded during the experiment.Results The mean serum concentration-time profile of ketamine and norketamine were fitted to a two-compartment open model with first order kinetics.The kinetic equation of ketamine and norketamine were ρt=121.760 e-0.025t＋ 0.980 e-0.002t＋4.579 e-0.021t and ρt=640.919 e-0.03t＋1.023 e-0.001t＋9.784 e-0.031t,respectively.The peak time and the peak concentration of ketamine in serum were（40.950±12.098） min and（9.015±1.344） μg/mL,respectively.The elimination half-time of ketamine in rabbits was（430.370±28.436） min.The serum and urine showed a middle relation in concentrations of ketamine during 30-240 min after drug administration.After oral administration ketamine to rabbits,the toxic symptom on the rabbits occurred at 30 min and disappeared after 120 min.Conclusion The toxicokinetics parameters and kinetic equation of ketamine and norketamine in rabbits may provide the theoretical basis for forensic identification of reasonable specimen collection and inferring the time of oral administration ketamine from the ketamine concentration in serum.

关 键 词：药动力学 GC-MS 氯胺酮 去甲氯胺酮 家兔 

分 类 号：R992[医药卫生—毒理学]