注射用穿琥宁乳剂在大鼠体内药代动力学及组织分布  

Pharmacokinetics and tissue distribution of Chuanhuning emuslion in rats

作　　者：禹玉洪 乔佛晓 玄京姬 李云清 李燕 

机构地区：[1]亚宝药业集团,亚宝药业北京药物研究院,北京101111 [2]中国医学科学院协和医学院药物研究所,北京100050

出　　处：《国际药学研究杂志》2014年第2期254-258,共5页Journal of International Pharmaceutical Research

基　　金：国家自然科学基金重大技术改造项目(2011ZX09201-201);山西省基础研究项目(2011011035-5)

摘　　要：目的研究自研新型注射用穿琥宁乳剂(CHE)在大鼠体内的药代动力学及组织分布情况。方法采用液相色谱-三重四级杆质谱联用技术(LC-MS/MS)建立脱水穿心莲内酯琥珀酸半酯(DAS)的检测方法;以市售普通穿琥宁注射液为参比制剂(CHR),研究CHE在大鼠体内的血浆药代动力学及组织分布情况;应用Winollin 6.2软件计算血浆药代动力学参数;以各时间点CHE与CHR组织浓度评价CHE的组织分布特点及靶向性。结果首先建立了一个适用于检测DAS的LCMS/MS方法;两种穿琥宁制剂在大鼠体内的药代动力学参数无显著性差异。尾静脉给予大鼠CHE或CHR 2 h后,CHE组DAS在靶组织肺中的浓度显著高于CHR。结论自研的CHE与CHR在大鼠体内的药代动力学过程相似,但可以增加DAS在靶器官肺中的浓度和作用时间,具有靶向增强作用。Objective To study the pharmacokinetics and tissue distribution of Chuanhuning-emulsion （CHE） in rats. Meth- ods The commercial ordinary Chuanhuning injection was used as the reference （CHR） to evaluate the pharmacokinetics and tissue distribution of CHE. After intravenous administration of CHE or CHR（40 mg/kg） in rats, the concentration of dehydroandrographolide succinate （DAS, the active ingredients of CHE in vivo） was detected by LC-MS/MS. Pharmacokinetic analysis was performed using WinNolin 6.2. Tissue distribution and targeting were evaluated through tissue concentrations. Results First, a suitable detection method was set up to study the pharmacokinetics of DAS. Second, there was no significant difference between CHR and CHE in the pharmacokinetic parameters. However, the concentrations of DAS in lungs of CHE group were higher than those in CHR group even at 2 h after iv administration of CHE or CHR. Conclusion CHE has a similar pharmacokinetic profile as CHR in rats. Furthermore, the cumulation of DAS in lungs is increased, which illustrates that CI-IE could enhance DAS targeted in lungs.

关 键 词：穿琥宁 乳剂 药代动力学 组织分布 

分 类 号：R96[医药卫生—药理学]