CAJ | 학술논문

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70 mg、140 mg和280 mg).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Topfit 2.0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3.125～10 000 μg·L~(-1)的血浆浓度范围内线性关系良好,最低定量浓度为3.125 μg·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:T_(1/2)为2.44、2.38、2.47 h;C_(max)为;1135.6、2841.1、3946.9 μg·L~(-1);T_(max)为1.35、1.26、1.39 h;AUC_(0～11 h)为1287.2、3337.8、5398.5 μg·h·L~(-1);AUC_(0-∞)为1300.7、3377.1、5453.9 μg·h·L~(-1);CL/F为1062.1、824.7、943.2 ml·min-1;V_d为219.9、167.1、212.0 L.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T_(1/2)差异无统计学意义,C_(max)、AUC_(0-11 h)与AUC_(0-∞)3个药动学参数随给药剂量的增加呈非比例上升趋势.
목적 연구건강지원자단제량구복수비계빈효낭후수비계빈적약대동역학.방법 9명건강남성지원자안랍정방설계분별구복3충제량수비계빈효낭(2립、4립화8립,상당우수비계빈70 mg、140 mg화280 mg).채용고효액상색보(HPLC)법측정인혈장중수비계빈적함량.응용Topfit 2.0연건계산주요약대동역학삼수.결과 재소건적방법하,수비계빈재3.125～10 000 μg·L~(-1)적혈장농도범위내선성관계량호,최저정량농도위3.125 μg·L~(-1).재3개급약제량하수비계빈적주요약대동역학삼수분별위:T_(1/2)위2.44、2.38、2.47 h;C_(max)위;1135.6、2841.1、3946.9 μg·L~(-1);T_(max)위1.35、1.26、1.39 h;AUC_(0～11 h)위1287.2、3337.8、5398.5 μg·h·L~(-1);AUC_(0-∞)위1300.7、3377.1、5453.9 μg·h·L~(-1);CL/F위1062.1、824.7、943.2 ml·min-1;V_d위219.9、167.1、212.0 L.결론 소건적방법구유령민도고、준학성호、조작간편등우점,능구만족수비계빈재인체내적약대동역학연구요구.3개제량하수비계빈재인체내적T_(1/2)차이무통계학의의,C_(max)、AUC_(0-11 h)여AUC_(0-∞)3개약동학삼수수급약제량적증가정비비례상승추세.
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.