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采用间接药效学模型和效应室模型两种药效学模型分别进行卡维地洛药动学与药效学关系研究,比较两种药效学模型的拟合程度。高效液相色谱法(荧光)测定20名健康志愿者单次口服20mg卡维地洛片后卡维地洛经时血药浓度,以DAS2.0实用药动学计算程序计算卡维地洛药动学参数。同时测定给药前后动脉收缩压和舒张压,计算降压效果。卡维地洛片主要药动学参数t1/2为(4.56±2.56)h,Cmax为(46.29±21.07)ng·mL-1,AUC0-∞为(173.76±87.36)ng·mL-1·h。间接药效模型主要参数Kin为(0.41±0.31)%h-1,Kout为(0.40±0.26)h-1,IC50为(24.40±21.10)ng·mL-1,AUE为(3.82±1.46)%h。效应室模型主要参数Ke0为(0.35±0.27)h-1,EC50为(24.30±24.30)ng·mL-1,AUE为(5.65±2.54)%h。该方法可用于卡维地洛片人体药动学研究。由AIC值可知,效应室模型可更好的应用于卡维地洛药动学-药效学结合研究。
Indirect pharmacodynamic model and effect chamber model were used to study the relationship between pharmacokinetics and pharmacodynamics of carvedilol respectively. The two models were compared. The plasma concentration of carvedilol in 20 healthy volunteers after a single oral administration of 20mg of carvedilol tablets was measured by high performance liquid chromatography (fluorescence), and the carvedilol was calculated by DAS2.0 practical pharmacokinetic calculation program Dynamic parameters. Simultaneous determination of arterial systolic and diastolic blood pressure before and after administration, calculated antihypertensive effect. The main pharmacokinetic parameters of carvedilol were t1 / 2 (4.56 ± 2.56) h, Cmax (46.29 ± 21.07) ng · mL-1 and AUC0-∞ of (173.76 ± 87.36) ng · mL- . The main parameters Kin of the indirect effect model were (0.41 ± 0.31)% h-1, Kout was (0.40 ± 0.26) h-1, IC50 was (24.40 ± 21.10) ng · mL-1 and AUE was (3.82 ± 1.46)% h The main parameters of effector chamber model were Ke0 of (0.35 ± 0.27) h-1, EC50 of (24.30 ± 24.30) ng · mL-1 and AUE of (5.65 ± 2.54)% h. This method can be used to study the pharmacokinetics of carvedilol tablets. From the AIC value, we can see that the effect chamber model can be better applied to the study of pharmacokinetics-pharmacodynamics of carvedilol.