连翘酯苷脂质体在雏鸡体内的药动学研究

Study on Pharmacokinetics of Forsythiaside Liposome in Chicks

试验旨在考察连翘酯苷脂质体静脉给药后在雏鸡体内的药物动力学和组织分布。将连翘酯苷脂质体与连翘酯苷水溶液分别以20mg/kg体重剂量给雏鸡静脉注射,于不同时间点取心脏、肝脏、脾脏、肺脏、肾脏组织和血液。HPLC法测定各时间点血液及各组织中连翘酯苷浓度。连翘酯苷脂质体和连翘酯苷溶液的血药浓度—时间曲线均符合二室开放模型,药动学参数消除半衰期(t1/2β)分别为(1.79±0.050)和(0.11±0.006)h,药时曲线下面积(AUC)分别为(39.95±2.32)和(4.26±0.39)(μg·h)/mL,体清除率(CLs)分别为(0.56±0.04)和(4.73±0.41)mg/(h·kg),连翘酯苷脂质体给药后在肝脏、脾脏、肺脏中的分布较连翘酯苷水溶液有明显提高。连翘酯苷脂质体明显改变了连翘酯苷的药动学行为,与游离药物相比,其有效延长了药物作用时间,在网状内皮系统丰富的组织有靶向性聚集作用。

The study was aimed to evaluate the pharmacokinetics and tissue distribution of forsythiaside liposome in chicks by intravenous administration. The pharmaeokinetics of chicks with intravenous administration of forsythiaside liposome and forsythiaside solution 20 mg/kg was studied and the concentrations of forsythiaside in heart, liver, spleen, lung, kidney and plasma were determined by HPLC. The plasma concentration-time curves of forsythiaside liposome and forsythiaside solution were both fit to the two-compartment model and the pharmacokinetic parameters were （1.79±0. 050） and （0.11±0. 006） h for t1/2β, （39.95±2.32） and （4.26±0.39） （μg. h）/mLforAUC, （0.56±0.04） and （4.73±0.41） mg/（h. kg） forCLs. Com- pared with the liposome to the solution, the drug distribution in liver, spleen and lung were obviously elevated. Compared with forsythiaside solution, the forsythiaside liposome could significantly prolong the resident time of forsythiaside in the blood cir- culating system and could be concentrated at the target tissue rich in the reticuloendothelial system.