甲氧滴滴涕及其代谢产物2,2-二(4-羟基苯基)-1,1,1-三氯乙烷在大鼠体内的毒代动力学

Toxicokinetics of methoxychlor and its metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane in rats

目的探讨甲氧滴滴涕(MXC)及其代谢产物2,2-二(4-羟基苯基)-1,1,1-三氯乙烷(HPTE)在大鼠体内的毒代动力学。方法雄性SD大鼠单次ig给予MXC 500 mg.kg-1染毒后,于不同时间点收集血液样本。应用高效液相色谱-紫外法测定大鼠血浆中MXC和HPTE的含量,用DAS 2.0软件的房室模型进行拟合,计算代谢动力学参数。结果 MXC的毒代动力学参数血浆最大浓度(cmax)为(5.52±1.21)mg.L-1;分布半衰期(t1/2α)为(4.12±1.21)h;消除半衰期(t1/2β)为(22.54±6.31)h;曲线下面积〔AUC(0-t)〕为(65.97±17.94)mg.h.L-1;AUC(0-∞)为(69.06±18.61)mg.h.L-1;清除率(Cl)为(7.94±2.31)L.h-1.kg-1;和表观分布容积(V)为(66.16±20.21)L.kg-1。代谢产物HPTE的毒代动力学参数cmax为(1.32±0.37)mg.L-1,t1/2α为(3.13±0.91)h;t1/2β为(31.12±10.91)h,AUC(0-t)为(14.69±2.99)mg.h.L-1,AUC(0-∞)为(17.23±3.66)mg.h.L-1,Cl为(30.14±6.09)L.h-1.kg-1,V为(232.55±36.44)L.kg-1。结论 MXC及其代谢产物HPTE的毒代动力学均符合二室模型。MXC和HPTE的清除半衰期均较长,易发生体内蓄积。

OBJECTIVE To explore toxicokinetics of methoxychlor（MXC）and its metabolite 2,2-bis-（p-hydroxyphenyl）-1,1,1-trichloroethane（HPTE） in rats.METHODS Eight male SD rats were ig given MXC 500 mg·kg-1 and plasma was collected at different time points before and after administration.MXC and HPTE concentrations in the plasma were determined by high performance liquid chromatography.The compartment model was fitted and toxicokinetic parameters were calculated by DAS 2.0 software.RESULTS The toxicokinetic parameters of MXC were as follows： cmax was（5.52±1.21）mg·L-1;t1/2α was（4.12±1.21）h;t1/2β was（22.54±6.31）h;AUC（0-t） was（65.97±17.94）mg·h·L-1;AUC（0-∞） was（69.06±18.61）mg·h·L-1;Cl was（7.94±2.31）L·h-1·kg-1;and V was（66.16±20.21）L·kg-1.The toxicokinetic parameters of HPTE were as follows： cmax was（1.32±0.37）mg·L-1;t1/2α was（3.13±0.91）h;t1/2β was（31.12±10.91）h;AUC（0-t） was（14.69±2.99）mg·h·L-1;AUC（0-∞） was（17.23±3.66）mg·h·L-1;Cl was（30.14±6.09）L·h-1·kg-1;and V was（232.55±36.44）L·kg-1.CONCLUSION The toxicokinetic profiles of MXC and HPTE in rats are both fitted to two-compartment model.MXC and HPTE may be accumulated easily due to their longer half-life clearance time.