建立丙戊酸钠在中国癫疒间患者中的群体药代动力学模型

发布时间：2018-08-19 08:36

【摘要】：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。
[Abstract]:Objective to establish a population pharmacokinetic model of Chinese epileptic patients taking sodium valproate to promote individual rational administration. Methods the blood concentration monitoring data and clinical data of 69 epileptic patients treated with sodium valproate were collected. A population pharmacokinetic model was established by using Phoenix NLME software (nl101, proportional residual model). The effects of covariables (sex, age, body mass, combined medication, etc.) on the apparent volume (Vd) and clearance (CL) of absorptive rate constant (Ka), were investigated. The final model was validated and evaluated by bootstrap method (NN500). Results the final pharmacokinetic model of population was: TvKA 2. 38 TvCL exp (畏 CL). The results showed that the average and median parameters of the model were the same as those of the model parameters, indicating that the model was stable, and the variables such as age, sex, body mass and combined medication could not be introduced into the final model. Conclusion the population pharmacokinetic model established in this study is consistent with the basic model and can provide the basis for rational individualized administration in clinic.
【作者单位】：第二军医大学长海医院药学部;第二军医大学长征医院药学部;
【基金】：国家自然科学基金(81302856) 上海市科学技术委员会计划项目(13ZR1413800)~~
【分类号】：R969.1

【相似文献】