藤甲酰苷纳米乳剂在大鼠体内药动学及组织分布研究

目的测定大鼠三个剂量（16.80、2.76、1.38 mg/kg）尾静脉注射藤甲酰苷纳米乳剂的血药浓度,比较他们之间的药动学行为;研究藤甲酰苷纳米乳剂在大鼠心、肝、脾、肺、肾中的分布情况。方法大鼠尾静脉注射三种不同浓度的藤甲酰苷纳米乳剂,采用高效液相法测定大鼠给药后不同时间点的血药浓度,应用3P87药动学程序对数据进行处理计算药动学参数;大鼠尾静脉注射大剂量（16.8 mg/kg）的藤甲酰苷纳米乳剂,采用相同方法,考察藤甲酰苷在预定时间的组织分布情况。结果藤甲酰苷纳米乳剂在大鼠体内的药动学过程符合双隔室模型,药动学参数分别如下：高剂量：T1/2α=18.47 min,AUC=8827.85 mg/L.min,Cls=0.001 903 mg/kg/（mg/L.min）,VRT=5293.11min.min;中剂量T1/2α=16.99 min,AUC=2905.02 mg/L.min,Cls=0.000 950 mg/kg/（mg/L.min）,VRT=3846.21 min.min;低剂量T1/2α=9.36 min,AUC=2089.00 mg/L.min,Cls=0.111 610 mg/kg/（mg/L.min）,VRT=3015.81 min.min药物在大鼠体内组织分布的最高浓度的大小顺序为脾、肺、肝、肾、心。结论藤甲酰苷在体内呈现非线性动力学消除过程,且体内分布快,起效迅速,消除也快,体内滞留时间短。藤甲酰苷在脾脏中分布最多,肺中较多,在心脏的分布最少。

Pharmacokinetics and tissue distribution of TJXG nano emulsion in rats

Objective To determine the plasma concentrations of TJXG （16.80, 2.76, 1.38 mg/kg） nanoemulsion after injected in caudal vein of rats, and to compare the pharmacokinetie behavior of the 3 groups, and to determine the distribution of TJXG in heart, liver, spleen, lung, and kidney of rats. Methods The concentration of TJXG in plasma were tested by HPLC after three different doses at various time points and the data was processed with the software 3P87. The concentration of TJXG （16.80 mg/kg） in tissues were tested by HPLC after a single does injection at predetermined time. Results Two compartment models were shown after TJXG nanoemulsion. The main pharmacokinetic parameters were presented respectively： high-dose： T1/2n=18.47 min, A UC= 8827.85 mg/L min, C/s=0.001 903 mg/kg/ （mg/L. rain）, VRT=5293.11 min. min; medium-dose： T1/2n= 16.99 min, A UC=2905.02 mg/L. min, Cls=0.000 950 mg/kg/ （mg/L. min）, VR T=3846.21 min. min; low-dose： Tlw=9.36 min, A UC=2089.00 rag/L- min, Cls = 0.111 610 mg/kg/（mg/ L.min, VRT=3015.81 min.min. The order of the highest concentration in the body size distribution was spleen, lung liver, kidney and heart. Conclusion The pharmacokineties of TJXG shows a nonlinear pharmacokinetics and a rapid distribution. The effect is fast,and the retention time is short. Most of TJXG is distributed in spleen, some also into lung, least of TJXG is distributed in heart.