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(t_max晚于血液，药-时曲线下面积(AUC_0-∞和达峰浓度(ρ_max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 striatum. 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. t_max， AUC_(0-∞ and ρ_max 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.