目的 評價生脈注射液中人參皂苷Rc在心絞痛患者體內(nèi)的藥代動力學(xué)-藥效動力學(xué)（PK-PD）相關(guān)性。方法 10名穩(wěn)定性心絞痛受試者連續(xù)靜脈滴注生脈注射液14 d，分別于給藥后不同時間點(diǎn)采集血漿樣品，采用液相色譜-串聯(lián)質(zhì)譜（LC-MS）法測定血漿中人參皂苷Rc的血藥濃度，繪制藥-時曲線，進(jìn)行非房室模型擬合并計算PK參數(shù)；以受試者的收縮壓（SBP）、舒張壓（DBP）及心率（HR）作為藥效指標(biāo)，進(jìn)行PK-PD結(jié)合模型的擬合，計算PK-PD參數(shù)。結(jié)果 人參皂苷Rc在心絞痛受試者體內(nèi)的PK符合二室模型，其降壓及加快HR的效應(yīng)滯后于血藥濃度，不與血藥濃度直接相關(guān)；效應(yīng)室濃度與藥效之間具有良好的相關(guān)性，血壓和HR的效應(yīng)模型分別符合Inhibitory Effect Sigmoid I_max和Sigmoid E_max模型。結(jié)論 成功建立了生脈注射液中人參皂苷Rc在心絞痛患者體內(nèi)的PK-PD結(jié)合模型，可有效地用于預(yù)測其血藥濃度和效應(yīng)，評價藥效物質(zhì)基礎(chǔ)。

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 I_max model and Sigmoid E_max 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.

國家"十二五"重大新藥創(chuàng)制項目（2012ZX09303-017）；國家臨床重點(diǎn)?？平ㄔO(shè)項目經(jīng)費(fèi)資助（2013年）；國家中醫(yī)藥管理局臨床中藥學(xué)重點(diǎn)學(xué)科（2009年）；遼寧中醫(yī)藥大學(xué)杏林學(xué)者青藍(lán)工程（2013年）