苦参碱微乳经皮给药在小鼠体内的药动学及组织分布研究  

Pharmacokinetics and Distribution of Microemulsion System for Transdermal Delivery of Matrine in Mouse

作　　者：魏红 张振[2] 牛晓方[3] 

机构地区：[1]山东医学高等专科学校,济南250002 [2]山东大学齐鲁医院临床药理研究所,济南250012 [3]菏泽市立医院药剂科,山东菏泽274000

出　　处：《中国药学杂志》2010年第24期1939-1943,共5页Chinese Pharmaceutical Journal

基　　金：山东省自然科学基金项目(Y2007C078)

摘　　要：-的建立小鼠血浆苦参碱的GC-MS联用分析法,测定药动学参数和组织分布。方法小鼠分别腹腔注射苦参碱注射液和经皮给苦参碱微乳,用GC-MS分析法分别测定血浆和各组织中苦参碱浓度,计算药动学参数和组织中苦参碱含量。结果苦参碱在32-800 ng.mL^-1内线性关系良好（r=0.999 5）,最低检出限量1 ng.mL^-1,日间和日内RSD均小于2.8%,提取回收率为72.2%-78.8%,方法回收率为92.1%-98.9%。苦参碱微乳经皮给药比苦参碱注射液腹腔注射,血药浓度稳定持久,具有显著差异（P〈0.01）;苦参碱微乳经皮给药后,在组织中的分布由高到低依次是肺、肾、脾、肝和心。结论本方法专属性、准确度、灵敏性高;微乳中苦参碱以零级动力学透过皮肤,可提供比注射剂更为稳定的血药浓度,具有开发应用前景。OBJECTIVE To develop a highly sensitive, simple and selective gas-chromatography mass spectrometry （GC/MS） method for investigating the pharmacokinetics and distribution of matrine in mouse plasma, and tissues respectively. METHODS The contents of matrine in mouse plasma and tissues were determined using GC/MS. The pharmacokinetic parameters were calculated by DAS 2.0. RESULTS The linearity was ranged from 32 to 800 ng ~ mL- ~ （ r --- 0. 999 5 ）. The RSDs （ % ） of within-day and between- day were all below 2. 8%. The absolute recovery was in the range of 72. 2% -78.8%. The method recovery was 92. 1% -98. 9%. The matfine-loaded mieroenmlsion built up more stable and persistent drug level than matrine injection（P 〈 0. 0l ）. After percutaneous administration of marine-loaded microemulsion, the sequence of contents of matrine in tissues was as follows ： lung 〉 kidney 〉 spleen 〉 liver 〉 heart. CONCLUSION The GC/MS method was successfully applied to quantify the low matrine concentration in plasma sam- pies and tissues, and suitable for its pharmacokinetic studies. The matrine-loaded microemulsion presented a permeation mode[ with zero-order kinetics. Furthermore, the matrine-loaded micruemulsion can build up a higher, more stable and persistent blood drug level than that of matrine injection. It have a good prospect of expMtation and utilization.

关 键 词：苦参碱 经皮吸收制剂 小鼠 药动学 组织分布 

分 类 号：R965.1[医药卫生—药理学]