摘要
目的评价生脉注射液中人参皂苷Rc在心绞痛患者体内的药代动力学-药效动力学(PK-PD)相关性。方法 10名稳定性心绞痛受试者连续静脉滴注生脉注射液14 d,分别于给药后不同时间点采集血浆样品,采用液相色谱-串联质谱(LC-MS)法测定血浆中人参皂苷Rc的血药浓度,绘制药-时曲线,进行非房室模型拟合并计算PK参数;以受试者的收缩压(SBP)、舒张压(DBP)及心率(HR)作为药效指标,进行PK-PD结合模型的拟合,计算PK-PD参数。结果人参皂苷Rc在心绞痛受试者体内的PK符合二室模型,其降压及加快HR的效应滞后于血药浓度,不与血药浓度直接相关;效应室浓度与药效之间具有良好的相关性,血压和HR的效应模型分别符合Inhibitory Effect Sigmoid Imax和Sigmoid Emax模型。结论成功建立了生脉注射液中人参皂苷Rc在心绞痛患者体内的PK-PD结合模型,可有效地用于预测其血药浓度和效应,评价药效物质基础。
Objective To evaluate the correlation of pharmacokinetics-pharmacodynamics（PK-PD） of ginsenoside Rc following the intravenous administration of Shengmai Injection in subjects with stable angina pectoris. Methods A total of 10 subjects with stable angina pectoris were selected with the intravenous administration of Shengmai Injection for 14 days. The plasma samples were collected at different time points, and the plasma concentration of ginsenoside Rc was determined by liquid chromatograph-mass spectrometry（LC/MS）. The concentration-time curves were drawn, and then the non-compartmental model were assessed to obtain the pharmacokinetic parameters. The systolic blood pressure（SBP）, diastolic blood pressure（DBP）, and the heart rate（HR） of the subjects were monitored, and the combined PK-PD model was established to calculate the PK-PD parameters. Results The pharmacokinetics of ginsenoside Rc conformed to a two-compartment model. The effects of lowing blood pressure and accelerating HR of Shengmai Injection lagged behind the concentrations of ginsenoside Rc in plasma, and indirectly related to plasma concentrations. The effects exhibited good correlation with ginsenoside Rc concentration in effect compartment. The relationship between effects and plasma concentrations fits Inhibitory Effect Imax model and Sigmoid Emax model, respectively. Conclusions This study successfully established the combined PK-PD model of ginsenoside Rc in subjects with angina pectoris, which can efficiently predict plasma concentration and effect, and evaluate the effective substance of Shengmai Injection.
作者
高小明
杨瑞
夏素霞
唐思
张世良
董晓茜
李国信
GAO xiaoming;YANG Rui;XIA Suxia;TANG Si;ZHANG Shiliang;DONG Xiaoqian;LI Guoxin(Academe of Traditional Chinese Medicine of Liaoning Province,Shenyang 110034,China)
出处
《药物评价研究》
CAS
2018年第7期1241-1245,1259,共6页
Drug Evaluation Research
基金
国家"十二五"重大新药创制项目(2012ZX09303-017)
国家临床重点专科建设项目经费资助(2013年)
国家中医药管理局临床中药学重点学科(2009年)
辽宁中医药大学杏林学者青蓝工程(2013年)
关键词
生脉注射液
人参皂苷Rc
心绞痛
液相色谱-串联质谱
药代动力学
药代动力学-药效动力学
Shengmai Injection
ginsenoside Rc
angina pectoris
liquid chromatograph-mass spectrometry （LC/MS）
pharmacokinetics
pharmacokinetics-pharmacodynamics （PK,PD）
