美托洛尔立体异构体在自发性高血压大鼠中的药代动力学-药效学建模
Pharmacokinetic-pharmacodynamic modeling of metoprolol stereoisomers in spontaneously hypertensive rat.
作者信息
Yin X X, Zhang Y D, Luo J P, Huang X P, Shen J P, Ding Y, Huang D K
机构信息
Department of Pharmacology, Nanjing Medical University, China.
出版信息
Zhongguo Yao Li Xue Bao. 1997 Mar;18(2):104-8.
AIM
To study the combined pharmacokinetic-pharmacodynamic (PK-PD) model of metoprolol stereoisomers, and compare their inhibitory effects on cardiovascular system in the spontaneously hypertensive rats (SHR).
METHODS
The drug concentration in plasma was measured by the reversed phase HPLC and the drug effects were recorded by polygraph. The pharmacokinetic parameters and the PK-PD model parameters were calculated.
RESULTS
The plasma concentration-time profiles were adequately described by two-compartment model. Differences of Vd between (+)-Met and (-)-Met were found. The relationships between effects and concentration of effect compartment were represented by the sigmoid-Emax model. The Css50 of Vmax, dp/dtmax, and HR inhibitory effects of (+)-Met were larger than those of (-)-Met.
CONCLUSION
Stereo-selective drug distribution and different potencies of the inhibitory effects of (+)-Met and (-)-Met existed in SHR.
目的
研究美托洛尔立体异构体的药代动力学 - 药效学（PK - PD）联合模型，并比较它们对自发性高血压大鼠（SHR）心血管系统的抑制作用。
方法
采用反相高效液相色谱法测定血浆中药物浓度，用多导记录仪记录药物效应。计算药代动力学参数和PK - PD模型参数。
结果
二室模型能较好地描述血浆浓度 - 时间曲线。发现（+）-美托洛尔和（-）-美托洛尔的分布容积（Vd）存在差异。效应与效应室浓度之间的关系用S型Emax模型表示。（+）-美托洛尔对最大反应速度（Vmax）、最大变化率（dp/dtmax）和心率抑制作用的半数稳态浓度（Css50）大于（-）-美托洛尔。
结论
在自发性高血压大鼠中存在美托洛尔立体异构体的立体选择性药物分布以及（+）-美托洛尔和（-）-美托洛尔抑制作用的不同效能。
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