磷酸川芎嗪乳剂在大鼠体内的药动学及组织分布研究

目的:通过研究磷酸川芎嗪乳剂在大鼠体内的药动学和组织分布,探究磷酸川芎嗪乳剂的生物利用度和脑靶向性。方法:大鼠静脉注射50 mg·kg-1磷酸川芎嗪制剂,给药后,在不同时间采血,最后切除大鼠心脏,肝脏,脾脏,肺,肾,和脑。所有样品均采用液相色谱-质谱/质谱联用法(HPLC/MS/MS)进行检测,用DAS 2.1.1软件使用非房室分析计算药动学参数。结果:与参比制剂(磷酸川芎嗪注射液)相比,乳剂制剂血浆中的药动学参数无显著差异。在血浆中,乳剂的AUC0-∞和Cmax分别为(4406.96±977.08)mg·L-1·min和(52.131±13.61)mg·L-1。组织分布研究发现磷酸川芎嗪乳剂较参比制剂在脑组织分布更多。结论:磷酸川芎嗪乳剂在心、肝、脾、肺、肾中有靶向趋势,比参比制剂更易分布在组织中。磷酸川芎嗪乳剂制剂具有脑靶向性。

Pharmacokinetics and tissue distribution of ligustrazine emulsion in rats

OBJECTIVE To study the pharmacokinetics and tissue distribution of ligustrazine emulsion in rats and explore the bioavailability and brain targeting of ligustrazine phosphate emulsion.METHODS Rats were injected with 50mg kg-1 phosphate.After administration, blood was collected at different time points. Finally, the heart, liver, spleen, lung, kidney and brain of rats were removed. All samples were detected by liquid chromatography-mass spectrometry/mass spectrometry (HPLC/MS/MS), and pharmacokinetic parameters were calculated using non-compartmental analysis using DAS 2.1.1 software.RESULTS There was no significant difference in pharmacokinetic parameters between the emulsion preparation and the preparation (ligustrazine phosphate injection). In plasma, the AUC_(0-∞) and C_max of emulsions were 4 406.96±977.08 mg·L^-1 min and 52.131±13.61 mg·L^-1 respectively. Tissue distribution study revealed that ligustrazine phosphate emulsion was more distributed in brain tissue than preparation.CONCLUSION Ligustrazine phosphate emulsion has a tendency of targeting in heart, liver, spleen, lung and kidney, and is more easily distributed in tissues than the preparation. Ligustrazine phosphate emulsion preparation has the property of brain targeting.