【作者】 赵晶；

【导师】 康世良；

【作者基本信息】 东北农业大学 ， 临床兽医学， 2000， 硕士

【摘要】 本实验分别按0．2mg／kgBW和0．6mg／kgBW单剂量对正常硒水平仔猪肌注和口服亚硒酸钠后，首次系统地研究了其血液中药物代谢动力学及体内抗氧化系统动态变化规律。实验结果表明： 1．血药动力学特征符合一级吸收二室开放模型，其理论方程为： C＝Ae^-αt＋Be^-βt-（A＋B）e^-Kat其主要动力学参数为：肌注：吸收半衰期(T_1／2KA)为0．0499hrs，达峰时间（T_p）为0．4237hrs，消除半衰期(T_1/2β)为271．9311hrs，药时曲线下面积（AUC）为 31．7260 Mg／L·Hrs，表观分布容积（V_d）为 2．4721L／kg；口服：吸收半衰期(T_1／2KA)为0．3075hrs，达峰时间（T_p）为2．1517hrs，消除半衰期(T_1／2β)为510．2706hrs，药时曲线下面积（AUC）为75．1460Mg／L·Hrs，表观分布容积（V_d）为5．5742L／kg。 2．根据单剂量药动学参数，计算多剂量给药参数，为临床治疗制定给药方案：肌注：先导剂量（D^*）为0．5089mg／kgBW，维持剂量（D₀）为 0．2 mg／kgBW，给药间隔（τ）为 192hrs，平均稳态血药浓度（C）为0．1652μg／ml；口服：先导剂量（D^*）为 1．2262mg／kgBW，维持剂量（D₀）为 0．6mg／kgBW，给药间隔（τ）为 480hrs，平均稳态血药浓度（C）为0．1566μg／ml。 3．健康仔猪体内抗氧化系统随机体硒水平的变化也发生相应变化，但与后者相比有一个明显的滞后期。给予一定量的硒后，体内的抗氧化能力并没有立即增强，SOD及T－AOC均经过相对于硒浓度来说较长一段时间后才开始显著上升，而GSH－P_X则是先降低而后又逐渐升高的；MDA的变化也明显滞后于硒浓度的变化。说明机体内抗氧化系统与硒水平之间存在着内在的规律性的联系。更多还原

【Abstract】 In this paper the pharmacokinetics of selenium in blood and dynamic regularity of itsantioxidation in the body of the health piglet were systematically studied for the first timeby means of the experiment under conditions that 0.2 mg/kgBW or 0.6 mg/kgBW ofsodium selenite were respectively used for im and po as the single dose. The results wereas follows:1.The characteristics of blood-pharmacokinetics conforms to 1-absorption and 2-department open model, the theoretical equation wasC＝Ae^-αt＋Be^-βt-（A＋B）e^-Katthe main parameters: for im, the half -life of absorption (T_1／2KA) was 0.0499 hrs, the time ofreaching maximum concentration （T_p） was 0.4237 hrs,the half -life of elimination (T_1/2βwas 27l .9311 hrs,the area under the curve （AUC） was 3l.7260 Mg/L.h, and the volume ofdistribution （V_d） was 2.4721L/kg; for po, the time of reaching maximum concentration（T_p） was 2.1517hrs, the half -life of elimination (T_1/2β was 510.2706 hrs, the area underthe curve （AUC） was 75.1460 Mg/L.h, and the volume of distribution （V_d） was 5.5742L/kg.2.The parameters of multiple doses were calculated for clinic treat based on thekinetic parameters of the single dose. For im, loading dose （D^*） was 0.5089 mg/kgBWmaintenance dose （D₀） was 0.2mg/kgBW, dosing internal （τ） was l92 hrs, and meansteady state blood level （C） was 0．1652μg／ml; For po, loading dose （D^*） was 1.2262 mg/kgBW, maintenance dose （D₀） was 0.6 mg/kgBW dosing internal （τ） was 480 hrs, and meansteady state blood level（C） was 0.1566μg／ml.3.The oxidant defense system in the health piglet varied along with the change of Selevel in the body and had an obvious lag time comparing with the latter. Theantioxidtion did nOt been immediately enhanced when a certain quanity of Se was supplied.Both SOD and TAOC began going up considerably after a longer period but GSH-Pxwas firstly fell down and then increasingly rose uP. The change in MDA was aPparentlylater than that in Se density.This showed that there was regular irmer link betWeen theoxidant defense system and Se concentration.更多还原