水飞蓟宾胶囊在中国健康志愿者体内的药代动力学研究

目的研究健康志愿者单剂量口服水飞蓟宾胶囊后水飞蓟宾的药代动力学。方法9名健康男性志愿者按拉丁方设计分别口服3种剂量水飞蓟宾胶囊(2粒、4粒和8粒,相当于水飞蓟宾70mg、140mg和280mg)。采用高效液相色谱(HPLC)法测定人血浆中水飞蓟宾的含量。应用Topfit2.0软件计算主要药代动力学参数。结果在所建的方法下,水飞蓟宾在3.125～10000μg.L-1的血浆浓度范围内线性关系良好,最低定量浓度为3.125μg.L-1。在3个给药剂量下水飞蓟宾的主要药代动力学参数分别为:T12为2.44、2.38、2.47h;Cmax为;1135.6、2841.1、3946.9μg.L-1;Tmax为1.35、1.26、1.39h;AUC0～11h为1287.2、3337.8、5398.5μg.h.L-1;AUC0-∞为1300.7、3377.1、5453.9μg.h.L-1;CL/F为1062.1、824.7、943.2ml.min-1;Vd为219.9、167.1、212.0L。结论所建的方法具有灵敏度高、准确性好、操作简便等优点,能够满足水飞蓟宾在人体内的药代动力学研究要求。3个剂量下水飞蓟宾在人体内的T12差异无统计学意义,Cmax、AUC0-11h与AUC0-∞3个药动学参数随给药剂量的增加呈非比例上升趋势。

Study on pharmacokinetics of silibinin capsule in Chinese healthy volunteers

Aim To investigate the pharmacokinetic characteristics of silibinin in Chinese healthy volunteers.Methods Nine Chinese male healthy volunteers were divided into receiving orally a single dose of silibinin capsule corresponded 70,140 and 280 mg of silibinin,respectively,in Latin square design study.After administration of silibinin capsule,the plasma concentrations were determined by HPLC with UV detection.The pharmacokinetic parameters were analyzed by Topfit 2.0 program.Results The linearity of this method was found to be from 3.125 to 10 000 μg·L~(-1) with a lower limit of quantitation(LLOQ) of 3.125 μg·L~(-1) for silibinin.The pharmacokinetic parameters were calculated as the follows:at the three different dosages(70,140 and 280 mg),T_(1/2) was 2.44,2.38 and 2.47 h;C_(max) was 1135.6,2841.1 and 3946.9 μg·L~(-1);T_(max) was 1.35,1.26 and 1.39 h;AUC_(0-11 h) was 1287.2,3337.8 and 5398.5 μg·h·L~(-1);AUC_(0-∞)was 1300.7,3377.1 and 5453.9 μg·h·L~(-1);CL/F was 1062.1,824.7 and 943.2 ml·min~(-1);And V_d was 219.9,167.1 and 212.0 L,respectively.Conclusions The developed method is shown to be sensitive,accurate and simple,and can satisfy the requirement of pharmacokinetic study of silibinin in human.The C_(max),AUC_(0-11 h) and AUC_(0-∞) of silibinin in Chinese healthy volunteers(in ranges of 40～120 mg)are fitted with non-linear kinetic model,while there are no significant differences in T_(1/2) at the three different dosages.