鞣花酸微球在家兔体内的药代动力学分析

Pharmacokinetics of Ellagic Acid Microspheres in Rabbits

目的:通过家兔口服鞣花酸微球研究其药动学特征。方法:采用锐孔法制备鞣花酸微球,采用HPLC测定鞣花酸含量,Agilent C18色谱柱(4.6 mm×250 mm,5μm),流动相乙腈-0.1%磷酸水溶液(23∶77),流速0.8 m L·min^(-1),进样量20μL,检测波长254 nm,柱温30℃。利用DAS 2.0软件分析鞣花酸微球和鞣花酸片的药代动力学参数差异。结果:鞣花酸线性范围0.01~1.50 mg·L^(-1)(r=0.999 4),最低检测限0.01 mg·L^(-1)。家兔口服给药后,鞣花酸的药-时曲线出现双峰,可能在家兔体内存在肝肠循环。鞣花酸微球的药动学特征符合二室模型,主要药动学参数分布半衰期(t1/2β)(7.683±2.762)h;消除半衰期(t1/2α)(7.161±1.275)h;达峰时间(t_(max))(3.00±0)h;药峰浓度(Cmax)(1.121±0.259)mg·L^(-1)。结论:鞣花酸微球化后,比鞣花酸片的作用时间更长,生物利用度显著提高。

Objective： To study on pharmacokinetic characteristics of ellagic acid microspheres in rabbits by oral administration. Method： Orifice method was used to prepare ellagic acid microspheres,HPLC was employed to determine the concentration of ellagic acid with acetonitrile-0. 1% phosphoric acid solution（ 23∶ 77） at a flow rate of 0. 8 m L·min-1,detection wavelength was set at 254 nm,column temperature was controlled at30 ℃. Pharmacokinetic parameters differences of ellagic acid microspheres and ellagic acid tablets were analyzed by DAS 2. 0. Result： The linear range of ellagic acid was within 0. 01-1. 50 mg·L-1 with r of 0. 999 4,quantitation limit was 0. 01 mg ·L-1. Plasma concentration-time curve of ellagic acid showed double peak, there may be enterohepatic circulation in rabbits. Pharmacokinetic of ellagic acid microspheres could be evaluated by twocompartment model. Main pharmacokinetic parameters were shown as t1 /2βof（ 7. 683 ± 2. 762） h,t1 /2αof（ 7. 161 ±1. 275） h,tmaxof（ 3. 00 ± 0） h and Cmaxof（ 1. 121 ± 0. 259） mg·L-1. Conclusion： By comparing with ellagic acid tablets,ellagic acid microspheres exhibits higher bioavailability and longer action duration in rabbits.