芎冰微乳不同给药方式的兔体内药动学研究

Pharmacokinetics of Xiongbing Microemulsion in Rabbit with Different Routes of Administration

目的:研究芎冰微乳中川芎嗪(TMP)以ig、iv2种不同给药方式在兔体内的药动学特性。方法:芎冰微乳分别ig和iv给药后,采用高效液相色谱法测定不同时间点TMP的血药浓度,用DAS2.1数据处理软件计算药动学参数。结果:TMP对照品检测浓度在0.062～6.200μg·mL-1范围内与其峰面积积分值呈良好线性关系。ig、iv给予TMP在体内药动学过程均符合二室模型,其主要药动学参数如下:t1/2α分别为7.618、2.842min,t1/2β分别为56.417、20.318min,V分别为3.161、0.411L·kg-1,Cl分别为0.069、0.027L·min-1·kg-1,AUC(0～∞)分别为55594.712、149207.814μg·min·L-1,MRT(0～∞)分别为76.356、24.805min;ig给药绝对生物利用度为37.26%。结论:芎冰微乳ig给药消除较慢,在体内滞留时间较长,但绝对生物利用度较低;而iv给予TMP分布迅速,但代谢也较快,体内作用时间较短,不利于药物的疗效发挥。

OBJECTIVE：To investigate pharmacokinetic characteristics of ligustrazine（tetramethylpyrazine as chemical name,TMP） in rabbit after intragastric（i.g.） and intravenous（i.v.） administration of Xiongbing microemulsion.METHODS：The plasma concentration of TMP was determined by HPLC after i.g.and i.v.administration.The data were processed by DAS 2.1 software to calculate the pharmacokinetic parameters.RESULTS：The linear range of TMP was 0.062-6.200 μg·mL-1.The pharmacokinetics of TMP was fitted to two compartment model after i.g.and i.v administration.The main pharmacokinetic parameters for TMP were as follow：t1/2α were 7.618 min vs.2.842 min,t1/2β were 56.417 min vs.20.318 min,V were 3.161 L·kg-1 vs.0.411 L·kg-1,Cl were 0.069 L·min-1·kg-1 vs.0.027 L·min-1·kg-1,AUC（0-∞） were 55 594.712 μg·min·L-1 vs.149 207.814 μg·min·L-1,MRT（0-∞） were 76.356 min vs.24.805 min.The absolute bioavailability of TMP was 37.26% after i.g.administration.CONCLUSION：TMP distribute slowly with i.g.administration and the mean residence time is long,while the absolute bioavailability is relatively low.On the contrary,TMP distributed rapidly with i.v.administration.There are rapid metabolism and short duration,which is not good for the efficacy of drugs.