经口染毒百草枯在家兔体内的毒代动力学研究

郭翔; 郭伟; 李添娣; 谢玉璇; 刘奋

doi:10.16369/j.oher.issn.1007-1326.2021.06.006

经口染毒百草枯在家兔体内的毒代动力学研究

Study on toxicokinetics of paraquat by gavage in rabbits

摘要

摘要:
目的探讨经口染毒百草枯在家兔体内的毒物代谢动力学过程。
方法分别以100 mg/kg和200 mg/kg的剂量给家兔灌胃染毒，于染毒后不同时间采集血液样本，应用液相色谱质谱法测定各样本中百草枯的含量，绘制浓度-时间曲线，并用DAS 3.0软件计算毒物代谢动力学参数。
结果以100 mg/kg剂量的百草枯（质量分数20%）经口染毒后（1.96 ± 2.41）h，家兔体内血液中百草枯浓度达到峰值，之后血药浓度迅速下降，非房室模型统计矩参数中峰质量浓度为（2.53 ± 0.84）mg/L、半衰期为（8.41 ± 1.89）h、浓度曲线下面积为（14.10 ± 3.21）mg/（L·h）。200 mg/kg百草枯经口染毒后（1.76 ± 1.10）h达峰，之后血药浓度迅速下降，非房室模型统计矩参数中峰浓度为（9.21 ± 4.43）mg/L、半衰期为（15.47 ± 12.11）h、浓度曲线下面积为（76.05 ± 34.30）mg/（L·h）。两组家兔血浆中百草枯达峰时间和平均留存时间的差异无统计学意义（P > 0.05）。
结论百草枯经口染毒在家兔体内的变化过程符合三室模型特征，获得了不同染毒剂量百草枯在家兔体内的毒物代谢动力学参数。

Abstract:
Objective To study the toxicokinetics of paraquat by gavage in rabbits.
Methods Rabbits were administrated by gavage at the doses of 100 mg/kg and 200 mg/kg respectively. Blood samples were collected at different times after gavage. The content of paraquat in each sample was determined by liquid chromatography-mass spectrometry, the concentration time curve was drawn, and the toxicokinetic parameters were calculated by Das 3.0 software.
Results In low dose group (100 mg/kg), the T_max was (1.96 ± 2.41) h, then the paraquat concentration rapidly decreased. The main toxicokinetics parameters were: C_max(2.53 ± 0.84)mg/L; t_1/2z (8.41 ± 1.89)h; AUC (14.10 ± 3.21)mg/(L·h). In high dose group(200 mg/kg), the T_max was(1.76 ± 1.10)h and then the paraquat concentration rapidly decreased. The main toxicokinetics parameters were: C_max (9.21 ± 4.43)mg/L; t_1/2z (15.47 ± 12.11)h; AUC 76.05 ± 34.30)mg/(L·h). There was no significant difference in the peak time and average retention time of paraquat in plasma between these two groups(P > 0.05).
Conclusions The results show that the paraquat is consistent with three-compartment model for oral exposure. Toxicokinetics parameters of paraquat by oral exposure in rabbits were obtained.

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