甲基苯丙胺在家兔体内的毒物代谢动力学研究

目的研究甲基苯丙胺及其代谢物苯丙胺在家兔体内的毒物代谢动力学行为。方法GC/MS法测定家兔灌胃甲基苯丙胺后不同时间点血、尿中甲基苯丙胺和代谢物苯丙胺浓度,采用3P97程序进行房室模型拟合以及毒物代谢动力学参数计算。结果甲基苯丙胺和苯丙胺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。甲基苯丙胺在家兔体内Cm ax为1.457 mg/L±0.094 mg/L,Tm ax为1.557h±0.078h,t1/2 ka、t1/2α和t1/2β分别为0.384h±0.052h、1.614h±0.036h和3.007h±0.430h,CL为1.769 L/h/kg±0.114 L/h/kg。甲基苯丙胺的毒物代谢动力学方程为:C t=2.767 e-0.746 t+1.454 e-0.234 t+4.119 e-1.746 t。结论甲基苯丙胺在家兔体内吸收、消除和代谢都较快。建立的甲基苯丙胺毒物代谢动力学方程和参数可为甲基苯丙胺分析的合理取样、从血药浓度推断服毒时间以及甲基苯丙胺滥用的法医学鉴定提供理论依据。

Toxicokinetics of methamphetamine in rabbits

Objective To study the Toxicokinetics of methamphetamine and its main metabolite amphetamine in rabbits.Methods After intragastric administration of the methamphetamine.HCl to the rabbits,the serum and urine samples were collected and analyzed by GC/MS.Compartment model and toxicokinetics parameters of methamphetamine and amphetamine were assessed by 3P97 program.Results The mean serum concentration-time profile of methamphetamine and amphetamine were fitted to a two-compartment open model with first order kinetics.The main toxicokinetic parameters of methamphetamine were as follows: Cmax was 1.457mg/L±0.094 mg/L,Tmax was 1.557h±0.078h,and CL was 1.769 L/h/kg±0.114 L/h/kg.The t1/2 ka,t1/2α and t1/2β was 0.384h±0.052h,1.614h±0.036h and 3.007h±0.430h,respectively.The kinetic equation of methamphetamine was Ct=2.767e-0.746t+1.454e-0.234t+4.119e-1.746t.Conclusion The absorption,elimination and metabolism of methamphetamine in rabbits were fast.The toxicokinetics parameters and kinetic equation of methamphetamine and its metabolite amphetamine in rabbits may provide the theoretical basis for forensic evaluating of reasonable specimen collection and infer the time of oral administration methamphetamine from the methamphetamine concentration in serum.