硫酸镁治疗妊娠高血压综合征的群体药动学一药效学

POPULATION PHARMACOKINETICS/PHARMACODYNAMICS OFMAGNESIUM SULFATE IN PREGNANCY INDUCED HYPEKTENSIVE GKAVIDAS TREATED WITH THE DRUG

用ＮｏＮＭＥＭ程序分析硫酸镁治疗妊娠高血压综合征患者的群体药动学－药效学，以快－慢速率相继静脉输注二室开放模型拟合６０例患者的群体药动学参数，以效应室与中央室连接的三室模型，用参数法拟合２６例患者的ＳｉｇｍｏｆｄＥ＿（ｍａｘ）药效学模型的群体参数。采用分光光度法测定血镁浓度（以给药前的基础值作调整），选择舒张压降低的百分率为药效指标。硫酸镁的群体药动学参数为：群体典型值Ｋ＿（１０）（ｈ￣（－１）），Ｋ＿（１２）（ｈ￣（－１）），Ｋ＿（２１）（ｈ￣（－１））和Ｖｃ（Ｌ）分别等于１．６２，２０．８，２．７０，２７．０，其个体间变异σ＿（Ｋ１０）（％），σ＿（Ｋ１２）（％），σ＿（Ｋ２１）（％），σ＿（Ｖｃ）（％）分别等于２５．７０，１４．１３，２４．３３，３４．０４，浓度的残差变异σ＿Ｅ（％）等于１５．０３。硫酸镁的群体药效学参数为：群体典型值Ｅ＿（ｍａｘ）（％），Ｃ＿（ｅ（５０））（μｇ·ｍｌ￣（－１）），ｖ，Ｋ＿（ｅｏ）（ｈ￣（－１））分别等于２８．７３，２８．３９，４．２２，０．４３。其个体间变异σ＿（Ｅｍａｘ）（％），σ＿（Ｃｅ（５０））（％），σ＿ｖ（％），σ＿（Ｋｅｏ）（％）分别等于５６．３２，６２?

NONMEM program was applied for analyzing population pharmacoki netics/pharmacodynamics of magnesium sulfate in pregnancy induced hypertensive patients treated with thedrug.A 2-compartment Open medel with fast and slow consecutive intravenous infusion was used toestimate population pharmacokinetics from 60 patients,A 3-compartment model comprised an effectcompartment linked to the central compartment,sigmoid Emax effect model and parametric methedwere used to estimate population pharmacodynamic parameters from 26 patients. Serum magnesiumconcen trati on was determined by spectr ophotometric method ant it was adjusted with basic valuedetermined before dosage. The diastolic blood pressure lowering effect was chosen as index of effect ofcardiovascular response.The population pharmacokinetic parameters of magnesium sulfate were:the standard value ofK_(10)(h￣(-1)),K_(12)(h￣(-1)),K_(21)(h￣(-1)),and Vc(L·kg￣(-1))were estimated to be l.62,20.8,2.70,and27.0 , respectively.Their interindividual varibilities were estimated to be 25.70%,14.13%,24.33%,and 34.04%,respectively.The residual error of concentrations was 15.03%,Thepopulation pharmacedynamic parameters of magnesium sulfate were:the standard value of E_(max)(%),Ce_(50)(μ· ml￣(-1)),v,and K_(eo)(h￣(-1))were estimated to be 28.73,28.39,4.22,and 0.43.Theirinterindividual variability were estimated to be 56.32%,62.24%,33.47%and 42.76%. Theresidual error of effect was 28.54%.