芮建中, 蔡明虹, 储小曼, 陈, 刚. NONMEM法估算中国癫痫患者苯妥英的群体药动学参数J. 药学学报, 1995, 30(3): 172-178.
引用本文: 芮建中, 蔡明虹, 储小曼, 陈, 刚. NONMEM法估算中国癫痫患者苯妥英的群体药动学参数J. 药学学报, 1995, 30(3): 172-178.
JZ Rui, MH Cai, XM Chu , G Chen, . NONMEM APPROACH FOR ESTIMATING POPULATION PHARMACOKINETIC PARAMETERS OF PHENYTOIN IN CHINESE EPILEPTICCJ. Acta Pharmaceutica Sinica, 1995, 30(3): 172-178.
Citation: JZ Rui, MH Cai, XM Chu , G Chen, . NONMEM APPROACH FOR ESTIMATING POPULATION PHARMACOKINETIC PARAMETERS OF PHENYTOIN IN CHINESE EPILEPTICCJ. Acta Pharmaceutica Sinica, 1995, 30(3): 172-178.

NONMEM法估算中国癫痫患者苯妥英的群体药动学参数

NONMEM APPROACH FOR ESTIMATING POPULATION PHARMACOKINETIC PARAMETERS OF PHENYTOIN IN CHINESE EPILEPTICC

  • 摘要: 临床上常规收集的161例门诊癫痫患者苯妥英(DPH)的每日剂量—稳态血药浓度数据258对,应用NONMEM程序一步估算其群体药动学参数(meansand、variances),并定量地分析体重、性别、合并用药对最大消除速率Vm(mg·d-1),年龄对米-曼氏常数Km(μg·ml-1)的影响。异性间DPH的Vm无显著差异,群体特征病人(体重60kg,年龄≥15a,未合并用苯巴比妥、安定或硝基安定)的Vm为439mg·d-1,Km为6.21μg·ml-1。体重对Vm的调整值为WT/60的0.57次方,合并用药时Vm增加8.4mg·d-1,年龄<15a则Km下降7%。

     

    Abstract: Routine clinical pharmacok inetic data collected from epileptic out-patients whoreceived phenytoin(PHT)were analysed to estimate population pharmacokinetic parameters.Therewere 258 steady-state serum phenytoin concentrations and associated dosage (mg·d-1)from 161out-patients.The data were analysed using NONMEM program.The influence of body weight,drugcombinations and sex on the maximum elimination rate(Vm)and age on the Michaelis-Mentenconstant(Km)were investigated. The Vm and Km of phenytoin in a 60 kg adult out- patient ,without combination with other drugs(phenobarbital,clonazepam or diazepam) were estimated to be 439 mg·d-1 and 6.21μg· ml-1,respectively. The best function adjusts Vm to the 0.57 power in proportion to body weight.The Km forpatients less than 15 years old was 7%less than that for adults. The Vm of patients treated withphenytoin combined with phenobarbital ,clonazepam or diazepam will increase 8.4 mg·d-1.

     

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