芮建中, 卓海通, 姜国华, 陈刚. NONMEM法分析肾移植患者环孢素A的群体药动学J. 药学学报, 1995, 30(4): 241-247.
引用本文: 芮建中, 卓海通, 姜国华, 陈刚. NONMEM法分析肾移植患者环孢素A的群体药动学J. 药学学报, 1995, 30(4): 241-247.
JZRui, HTzhuo, GH Jiang ,GChen, . EVALUATION OFPOPULATION PHARMACOKINETICS OF CYCLOSPORIN A IN RENAL TRANSPLANTATION PATIENTSWITHNONMEMJ. Acta Pharmaceutica Sinica, 1995, 30(4): 241-247.
Citation: JZRui, HTzhuo, GH Jiang ,GChen, . EVALUATION OFPOPULATION PHARMACOKINETICS OF CYCLOSPORIN A IN RENAL TRANSPLANTATION PATIENTSWITHNONMEMJ. Acta Pharmaceutica Sinica, 1995, 30(4): 241-247.

NONMEM法分析肾移植患者环孢素A的群体药动学

EVALUATION OFPOPULATION PHARMACOKINETICS OF CYCLOSPORIN A IN RENAL TRANSPLANTATION PATIENTSWITHNONMEM

  • 摘要: 用HPLC和FPIA法(单克隆抗体)测定全血中环孢素A(CsA)浓度,收集临床60例肾移植患者牛奶送服CsA后浓度数据281点,应用NONMEM程序一步法估算其群体药动学参数,并定量地分析体重、年龄、性别,长期用药对清除率的影响。按口服吸收一室开放模型估算的群体药动学参数为:清除率CL(L·h-1)、表现分布容积Vd(L)和口服吸收速率常数Ka(h-1)分别等于59.8,227及1.28,其个体间变异QCL(%),QVL(%)及QKa(%)分别为30.27,29.02和75.10,浓度观察值与模型预测值的残差变异QE(%)等于31.19固定效应与CL的定量关系为:以体重的0.03倍加法调整,男性较女性患者增加4.31,长期用药患者下降12.7。

     

    Abstract: NONMEM program was applied for estimating population pharmacokineticparameters of cyclosporin A(CsA).The influence of body weight,age,sex and drug administrationhistory on clearance were investigated.There were 281 CsA concentrations in whole blood from 60cl inical renal transplantation patients.Samples were analysed by HPLC and FPIA(TDx,Abbett,monoclonal antibod). One conipartment open model with first-order absorption and elimination was used to analyse thedata,Population mean values of CL(L·h-1),Vd(L)and Ka(h-1 )were 5,227,and 1.28respectively.The interindividual variations of CL,Vd,and Kawere 3.27%,29.01%,and75.10%respectively.The residual error was 31.19%。The adjustment value of weight to clearancewas 0.03 times with additional model.CL increased.3l in male l)atients,and decreased l2.7 whenpatients were treated with CsA for a long time.

     

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