摘要
通过对20例重度妊高征患者采用快慢速率相继静脉输注硫酸镁进行治疗,根据Sheiner等提出的效应室模型分析理论,运用药效学模拟技术,对硫酸镁降低舒张压的效应进行研究,探讨临床药效学特征,揭示心血管效应的动态变化规律.以舒张压的变化率作为药效指标,测定不同时间点的血清镁浓度,同时测量患者的血压变化.假定效应室以一级动力学过程与二房室模型相连,药物以一级速率常数Ke从效应室中消除,药效分别按线性模型、E_(max)模型、S型E_(max)模型在计算机上运用PK-PD程序进行拟合.结果表明:反映血管周围阻力的舒张压是一项简单和合适的临床指标,血清镁与舒张压降低之间不呈平行关系;S型E_(max)模型能较好地描述镁药效的经时变化,该模型拟合出的效应值与效应观察值之间有着良好的相关性,与其它两种药效学模型比较有非常显著的差异;用药后1～3h有较好的降压效果,用药后第8h药效接近峰值,舒张压的降低一直维持至输注停止后7h,效应室的消除速率常数K_(eo)为0.37h^(-1),介于快处置相和慢处置相速率常数(分别为α=4.85h^(-1)和β=0.20h^(-1))之间,药物从效应室中的消除与其在血液中的消除相平行,而药物效应部位浓度的时间过程与组织分布不一致,从而证明药动学过程假想的不足,支持效应室的存在;
Pharmacodynamic modeling technique was used to analyze the time course of antihypertensive effect(Pharmacodynamics models) of magnesium in 20 cases with severe pregnancy induced hypertension. Thediastolic blood pressure lowering effect was chosen as index of effect of magnesium for cardiovascularresponsiveness. A computer-program based on the effect compartment model theory was used to accordwith the effect. The unparallelism of concentration with effect suggested that the equilibration betweenserum concentration and the effect site was delayed. The effect values were simulated to linear ,Emax. andsigmodial Emax effect model respectively and the result showed that the sigmoidal Emax model was mostsuitable to describe the relationship between the concentration in effect compartment and observed effect. The elimination rate constant from effect compartment(Keo) was 0.37h-1 ,the equilibration half-time(Te)was 1.87 b.y was 4.60(range: 1. 41~9.30). The time duration of decreasing the diastolicblood pressure was 1 13 h , the peak time was 8 h ,The elimination of drug from effect compartment was proportional to that from the central one and the time course of drug accumulation at the effect site could be predicted since the serum concentration changed.
关键词
妊娠高血压
综合征
硫酸镁
药理学
<Keyword>Clinical pharmacodynamics Pharmacodynamic Model Pregnancy induced hypertension Magnesium Sulfate Blood pressure
