帕金森病模型大鼠血液和纹状体细胞外液左旋多巴药动学同步研究  

Synchronous Pharmacokinetics Study on Levodopa in Parkinson′s Disease Rats Blood and Extracellular Fluids of Striatum

作　　者：孙晓芳[1] 王丹巧[2] 吴兆恩[2] 李鹏[2] 王志国[2] 牛建昭[1] 王继峰[1] 王巍[3] 

机构地区：[1]北京中医药大学基础医学院,北京100029 [2]中国中医科学院医学实验中心,北京100700 [3]中国中医科学院西苑医院,北京100091

出　　处：《中国药学杂志》2011年第8期610-614,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30772780);中国中医科学院基本科研业务费自主选题资助项目(ZZ2006037)

摘　　要：目的采用清醒自由活动大鼠血-脑双位点微透析采样的方法,同步探讨左旋多巴(L-DOPA)在帕金森病(PD)大鼠血液和纹状体细胞外液药物浓度随时间变化的规律。方法 SD大鼠随机分为5组,对照组、模型组、高剂量对照组、高剂量模型组和低剂量模型组,脑内注射6-羟基多巴胺(6-OHDA)造模,血-脑双位点微透析采样,分别用高效液相-荧光法(HPLC-FLD)、高效液相-电化学法(HPLC-ED)检测血、纹状体细胞外液L-DOPA浓度。应用DAS软件拟合药动学参数。结果 PD大鼠腹腔给药后,药物迅速吸收入血,并通过血脑屏障进入纹状体。血液、纹状体细胞外液L-DOPA药-时曲线符合一室模型;纹状体细胞外液L-DOPA的达峰时间(tmax)晚于血液,药-时曲线下面积(AUC0-∞)和达峰浓度(ρmax)小于血液。结论清醒PD模型大鼠纹状体细胞外液药动学过程与血液相比存在时间滞后;血、脑药物浓度与给药剂量存在依赖关系,血液药动学行为不能完全反映纹状体中的情况。OBJECTIVE To synchronous investigate the drug concentration-time profiles of levodopa（L-DOPA） in blood and striatal extracellular fluids in striatum of Parkinson＇s disease（PD） rats by simultaneous blood-brain microdialysis in unrestriced conscious rats. METHODS SD rats were randomly divided into 5 groups ： control group, and model group, control high dose group, and model high dose group, model low dose group. The Parkinson＇s disease rats were induced by injecting 6-hydrodopamine（6-OHDA） into striarum. Blood-brain microdialysis technique was used for simultaneously sampling. High performance liquid chromatography-fluorescence detector（HPLC-FLD） and high performance liquid chromatography-electrochemical detector（HPLC-ED） were used to determince the concentration of L-DOPA in blood and striatum, respectively. The data were analyzed with DAS program. RESULTS L-DOPA was absorbed in blood rapidly after intraperitoneal injection, then entered striatum through blood brain barrier. Both the blood and striatum concentration-time profiles of L-DOPA were described by one compartment model, tmax, AUC（0-∞） and Pmax in striatum were significantly different from that in blood. CONCLUSION The pharmacokinetics of L-DOPA in striatum lagged behind that in blood. Both blood and brain drug concentration are dose-dependent. The pharmacokinetics of L-DOPA in blood con not reflected completely that in striatum.

关 键 词：脑内微透析 血液微透析 左旋多巴 药动学 6-羟基多巴胺 

分 类 号：R965[医药卫生—药理学]