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目的建立中国癫疒间患者服用丙戊酸钠的群体药代动力学模型,促进个体化合理给药。方法收集69例癫疒间患者服用丙戊酸钠后的血药浓度监测数据和临床资料。应用Phoenix NLME软件建立群体药代动力学模型(n=101,选择比例型残差模型表示),考察协变量(性别、年龄、体质量、合并用药等)对吸收速率常数(Ka)、表观分布容积(Vd)与清除率(CL)的影响。通过自举法对最终模型进行验证及评价(n=500)。结果群体药代动力学最终模型为:TvKa=2.38,V=TvV,CL=TvCL·exp(ηCL)。自举500次验证模型,结果显示稳健率100%,得到的参数平均值、中位数均与模型参数结果一致,说明模型比较稳定;年龄、性别、体质量、合并用药等变量无法引入最终模型中。结论本研究建立的群体药代动力学模型与基础模型一致,可为临床合理的个体化给药提供依据。
Objective To establish a population pharmacokinetic model of sodium valproate in patients with epilepsy in China and to promote individual rational administration. Methods Blood samples were collected from 69 patients with epilepsy after taking sodium valproate to monitor blood concentration and clinical data. The population pharmacokinetic model (n = 101, select proportional residual model) was established using Phoenix NLME software to investigate the effect of covariate (sex, age, body weight, drug combination) on the absorption rate constant Effect of distribution volume (Vd) and clearance (CL). The final model was validated and evaluated through bootstrapping (n = 500). Results The final population pharmacokinetic model was: TvKa = 2.38, V = TvV, CL = TvCL · exp (ηCL). Bootstrap 500 validation models, the results showed that the robust rate of 100%, the average and median parameters were consistent with the results of the model parameters, indicating that the model is relatively stable; age, gender, body weight, combined medication and other variables can not be introduced into the final model in. Conclusion The population pharmacokinetic model established in this study is consistent with the basic model and can provide the basis for clinical rational individualized administration.