甲基苯丙胺和氯胺酮在家兔体内毒代动力学及相互影响

A study on toxicokinetics of methamphetamine and ketamine and their interaction in rabbits

目的比较家兔单独静脉注射甲基苯丙胺、氯胺酮及二种药物联合静注时的毒物代谢动力学过程,评价二种药物毒代动力学的相互作用。方法单用甲基苯丙胺组以3mg/kg剂量家兔静脉注射甲基苯丙胺,单用氯胺酮组以30mg/kg剂量家兔静脉注射氯胺酮,合用组以相同剂量同时注射两种药物。分别于给药后不同时间点收集血浆标本,测定各时间点药物浓度,WinNonLin软件拟合毒代动力学房室模型并计算参数。结果甲基苯丙胺在家兔体内的毒代动力学过程呈一级动力学特征,符合单室模型,合用氯胺酮后不改变其模型类型。氯胺酮在家兔体内的毒代动力学过程呈一级动力学特征,符合单室模型,合用甲基苯丙胺后符合二室模型。结论甲基苯丙胺和氯胺酮可以相互延缓其在体内的消除过程,增加彼此在体内的吸收,从而延长作用时间。

Objective To study the toxicokinetic profiles of methamphetamine or ketamine alone and coadministration of both drugs by intravenous injection in rabbits and interaction between methamphetamine and ketamine in rabbits.Methods The rabbits were given intravenously methamphetamine hydrochloride with a dose of 3mg/kg（5 rabbits）,or ketamine hydrochloride with a dose of 30mg/kg（5 rabbits）,or both drugs with the same dose（5 rabbits）,respectively.Blood was sampled through carotid artery at 0,10,20,30,40,50,60,70,80,90,120,150 and 180min after drug administration.Concentration of methamphetamine or ketamine was determined by GC or GC/MS.Toxicokinetic compartment model and parameters were assessed by WinNonLin program.Results The mean plasma concentration-time profile of methamphetamine was characterized by first order kinetics in a one-compartment model and not affected by coadministration with ketamine.The mean plasma concentration-time profile of ketamine was also characterized by a one-compartment model,but presented as a two-compartment model after coadministration with methamphetamine.Conclusion Interaction between methamphetamine and ketamine may delay their eliminating process,and prolong their pharmacodynamic phases.