苯嗪草酮单次给药在大鼠体内的毒代动力学规律及其组织分布

Toxicokinetic Study on Single Dose of Metamitron to Rat

[目的]研究苯嗪草酮(metamitron)在大鼠体内的毒代动力学规律及组织分布。[方法]采用高效液相色谱紫外检测法测定大鼠血液、组织、粪尿样品中苯嗪草酮原药浓度,计算毒代动力学参数。[结果]苯嗪草酮在雌、雄大鼠体内符合血管外给药一级吸收一室模型。主要毒代动力学参数包括:吸收半衰期为0.77h和0.69h,消除半衰期为7.34h和2.12h,参数消除率为0.78L(/h.kg)和2.59L(/h.kg),表观分布容积为10.75L/kg和8.33L/kg,药时曲线下面积为1594.07mg(/L.h)和975.36mg(/L.h);雄性药动学方程为C=8.79(e-0.39t-e-1.04t),雌性大鼠药动学方程为C=4.96(e-0.13t-e-2.01t)。大鼠灌胃苯嗪草酮4h后,在肝、心、脑脂肪中的浓度高于血清中的浓度,各组织的浓度最高值时的顺序依次是:肝>心>脑>脾>脂肪>肌肉>肺>肾>睾丸。大鼠通过粪便方式排出苯嗪草酮7d累积排泄量占总剂量的71.44%,尿液为8.91%。[结论]在该试验条件下,苯嗪草酮经灌胃吸收迅速,消除较快,在体内分布广泛,主要通过粪便方式排出体外。

[ Objective i To study toxicokinetic characteristics of metamitron in rat plasma and tissuse. [ Methods ] High performance liquid chromatography coupled with ultraviolet detector method was used to determine the concentration of metamitron in rat blood, tissues, and excrement samples, and toxicokinetic parameters were analyzed. [ Results ] The serum drug-time curves were consistent with first-order models of both male and female rats. The main toxicokinetic parameters for female and male rats were： tl/2 （Ka）, 0.77h and 0.69h; tl/2（Ke）, 7.34h and 2.12h; CL, 0.78L/（h· kg） and 2.59L（/h · kg）; Vd, 10.75L/kg and 8.33 L/kg; AUC, 1 594.07 mg/（L · h） and 975.36 mg/（L · h）. The kinetic equations for male and female rats were C=8.79 （e-0.39t-e-1.04t and C=4.96 （e-0.13t-e-2.01t）, respectively. Concentrations of metamitron in liver, heart, and fat tissue were higher than those in plasma at the 4th hour after stomach lavaging with metamitron to the rats. The order of peak metamitron concentrations in rat tissues was： liver 〉 heart 〉 brain 〉 spleen 〉 fat 〉 muscle 〉 lung 〉 kidney 〉 testicle. The 7-day cumulative meramitron in feces and urine were 71.44% and 8.91%, respectively. [ Conclusion ] Quick gavage absorption, wide distribution to varied tissues and organs, and elimination via feces and urine of metamitron are observed under the reported experimental settings.