水飞蓟宾原料药、利加隆、水林佳大鼠体内药物动力学研究

Pharmacokinetics of silybin,Legalon and Shuilinjia in rats

目的:研究水飞蓟宾原料药、水飞蓟宾市售胶囊利加隆、水林佳在大鼠体内的药动学过程和药动学参数。方法:建立水飞蓟宾在大鼠血浆中的HPLC检测方法。考察大鼠给予水飞蓟宾原料药及市售胶囊后血药浓度变化。结果:水飞蓟宾质量浓度在10~10000ng/mL范围内线性关系良好;定量下限为10ng/mL;日内和日间精密度RSD小于2.5%;准确度为100.2%~102.3%;提取回收率为82.3%~87.4%。大鼠灌胃给予原料药、利加隆和水林佳后,水飞蓟宾在大鼠体内消除半衰期(t_(1/2))分别为(18.7±9.6)h、(10.0±5.6)h、(9.9±0.9)h,血药浓度曲线下面积(AUC_(0~12))分别为(1459.0±321.2)ng·h/mL、(5268.2±681.3)ng·h/mL、(8179.3±1070.0)ng·h/mL,达峰浓度(C_(max))分别为(61.8±11.2)ng/mL、(495.3±123.5)ng/mL、(5895.8±2487.1)ng/mL。利加隆、水林佳与原料药相比,其相对生物利用度分别为361.0%和560.6%。结论:水飞蓟宾口服生物利用度低,市售胶囊均显著提高水飞蓟素相对生物利用度。

Objective:To study the pharmacokinetics and pharmacokinetic parameter of silybin,Legalon^(R)and Shuilinjia^(R)in rats.Methods:HPLC was established for detecting plasma concentration of silybin and investigating its pharmacokinetics in rats.Results:The linear calibration curve was obtained in the range of 10~10000 ng/mL for silybin,and the lower limit of quantitation was10 ng/mL.The RSDof intra-day and inter-day assays were less than 2.5%and the accuracy of three different concentrations was in the range from 100.2%to 102.3%.The extraction recovery of silybin from rat plasma was from 82.3%to 87.4%.The main pharmacokinetics parameters of silybin,Legalon^(R)and Shuilinjia^(R)were shown as follows:t_(1/2)(18.7±9.6),(10.0±5.6),and(9.9±0.9)h;AUC_(0~12)(1459.0±321.2),(5268.2±681.3)and(8179.3±1070.0)ng·h/mL,repectively;C_(max)(61.8±11.2)ng/mL,(495.3±123.5)ng/mL,and(5895.8±2487.1)ng/mL,repectively.Compared to crude drug,the relative bioavailability of Legalon^(R)and Shuilinjia^(R)were about 361.0%and 560.6%.Conclusion:The oral bioavailability of silybin was low.The relative bioavailability of silybin was significantly inproved in all silybin capsules.