摘要
目的研究四逆汤中8种成分在大鼠体内的药动学特征。方法SD大鼠灌服四逆汤水煎液(4 g·kg^(-1)),不同时间点采血,LC-MS/MS法测定血药浓度,并计算药动学参数。结果乌头碱、新乌头碱、次乌头碱、苯甲酰新乌头原碱、苯甲酰次乌头原碱、甘草苷、甘草酸和甘草次酸在相应浓度范围内线性关系良好(r>0.995),日内、日间RSD均<12%,达峰时间(T_(max))分别为(1.08±0.38)h、(1.08±0.38)h、(0.61±0.35)h、(1.32±0.76)h、(1.67±0.29)h、(0.25±0.12)h、(2.50±1.32)h和(10.67±2.31)h;消除半衰期(t_(1/2))分别为(2.68±0.78)h、(2.61±1.68)h、(5.56±3.15)h、(2.47±1.25)h、(9.12±4.89)h、(0.89±0.22)h、(10.50±6.84)h和(7.20±2.97)h;达峰浓度(C_(max))分别为(0.03±0.01)ng·mL^(-1)、(0.02±0.003)ng·mL^(-1)、(1.11±0.15)ng·mL^(-1)、(0.21±0.07)ng·mL^(-1)、(0.06±0.03)ng·mL^(-1)、(14.87±3.84)ng·mL^(-1)、(72.60±35.06)ng·mL^(-1)和(249.83±130.32)ng·mL^(-1);浓度-时间曲线下面积(AUC_(0-t))分别为(0.09±0.02)ng·h·mL^(-1)、(0.05±0.009)ng·h·mL^(-1)、(4.09±0.67)ng·h·mL^(-1)、(0.99±0.06)ng·h·mL^(-1)、(0.42±0.03)ng·h·mL^(-1)、(19.04±2.77)ng·h·mL^(-1)、(376.23±48.35)ng·h·mL^(-1)和(2726.65±1172.56)ng·h·mL^(-1)。结论本方法方便、快速,可用于四逆汤各成分的药动学研究。
Objective To investigate the pharmacokinetic characters of eight active components of Sini Decoction(四逆汤,SND)in rats plasma.Methods SD rats were orally administered SND aqueous extract(4 g·kg^(-1))and blood samples were collected at different time points.The plasma concentrations were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters were calculated.Results All the constituents showed the good linear relationship(r>0.995),RSDs of inta-day and inter-day were all lower than 12%.The pharmacokinetic parameters of aconitine,mesaconitine,hypaconitine,benzoylmesaconine,benzoylhypaconine,liquiritin,glycyrrhizic acid and glycyrrhetinicacid were as follows:the values of T_(max) were(1.08±0.38)h,(1.08±0.38)h,(0.61±0.35)h,(1.32±0.76)h,(1.67±0.29)h,(0.25±0.12)h,(2.50±1.32)h and(10.67±2.31)h;the values of t 1/2 were(2.68±0.78)h,(2.61±1.68)h,(5.56±3.15)h,(2.47±1.25)h,(9.12±4.89)h,(0.89±0.22)h,(10.50±6.84)h and(7.20±2.97)h;the values of C_(max) were(0.03±0.01)ng·mL^(-1),(0.02±0.003)ng·mL^(-1),(1.11±0.15)ng·mL^(-1),(0.21±0.07)ng·mL^(-1),(0.06±0.03)ng·mL^(-1),(14.87±3.84)ng·mL^(-1),(72.60±35.06)ng·mL^(-1)and(249.83±130.32)ng·mL^(-1);the values of AUC_(0-t) were(0.09±0.02)ng·h·mL^(-1),(0.05±0.009)ng·h·mL^(-1),(4.09±0.67)ng·h·mL^(-1),(0.99±0.06)ng·h·mL^(-1),(0.42±0.03)ng·h·mL^(-1),(19.04±2.77)ng·h·mL^(-1),(376.23±48.35)ng·h·mL^(-1)and(2726.65±1172.56)ng·h·mL^(-1).Conclusion The method is convenient and rapid,and can be used for the pharmacokinetic study of the components of SND in vivo.
作者
缪萍
裘福荣
曾金
贺敏
王猛猛
陈文文
沈淑娇
符胜光
蒋健
MIAO Ping;QIU Furong;ZENG Jin;HE Min;WANG Mengmeng;CHEN Wenwen;SHEN Shujiao;FU Shengguang;JIANG Jian(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;The Affiliated People′s Hospital of Ningbo University,Ningbo 315040,Zhejiang,China;Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《辽宁中医杂志》
CAS
北大核心
2024年第1期205-209,I0008,共6页
Liaoning Journal of Traditional Chinese Medicine
基金
国家“十二五”重大新药创制-创新药物研究开发技术平台建设项目(2012ZX09303009-001)
上海市教委重点学科中药临床药理学项目(J50303)。
作者简介
缪萍(1986-),女,浙江人,主治中医师,博士,研究方向:中医内科临床与基础研究;通讯作者:蒋健(1956-2023),男,江苏人,主任医师、教授,博士生导师,博士,研究方向:中西医结合治疗消化系统疾病,E-mail:jiangjiansg@126.com。
