Guo Jinlin, Huo Yayu, Li Fang, Li Yuanping, Guo Zhaojun, Han Huaqing, Zhou Yuhong
Department of Pharmacy, Shanxi Provincial People's Hospital, Taiyuan, China.
Department of Pharmacy, Shanxi Bethune Hospital & Shanxi Academy of Medical Sciences, Taiyuan, China.
J Int Med Res. 2020 Aug;48(8):300060520952281. doi: 10.1177/0300060520952281.
This prospective study aimed to establish the valproic acid (VPA) population pharmacokinetic model in Chinese patients and realise personalised medication on the basis of population pharmacokinetics.
The patients' clinical information and VPA plasma concentrations were collected from The General Hospital of Taiyuan Iron & Steel (Group) Corporation (TISCO). Nonlinear mixed-effect modelling was used to build the population pharmacokinetic model. To characterise the pharmacokinetic data, a one-compartment pharmacokinetic model with first-order absorption and elimination was used. The first-order conditional estimation with η-ε interaction was applied throughout the model-developing procedure. The absorption rate constant (Ka) was fixed at 2.38 hour, and the impact of covariates on clearance and apparent volume of distribution were also explored. Medical records of 60 inpatients were reviewed prospectively and the objective function value (OFV) of the base model and final model were 851.813 and 817.622, respectively.
Gender was identified as the covariate that had a significant impact on the volume of distribution, and albumin and CYP2C19 genotypes influenced clearance.
Bootstrap and VPC indicated that a reliable model had been developed that was based on the simulation results, and a simple-to-use dosage regimen table was created to guide clinicians for VPA drug dosing.
本前瞻性研究旨在建立中国患者丙戊酸（VPA）群体药代动力学模型，并基于群体药代动力学实现个体化给药。
从太原钢铁（集团）有限公司总医院收集患者的临床信息和VPA血药浓度。采用非线性混合效应建模构建群体药代动力学模型。为表征药代动力学数据，使用具有一级吸收和消除的单室药代动力学模型。在整个模型开发过程中应用具有η-ε交互作用的一级条件估计。吸收速率常数（Ka）固定为2.38小时，并探讨协变量对清除率和表观分布容积的影响。前瞻性回顾了60例住院患者的病历，基础模型和最终模型的目标函数值（OFV）分别为851.813和817.622。
性别被确定为对分布容积有显著影响的协变量，白蛋白和CYP2C19基因型影响清除率。
自举法和VPC表明，基于模拟结果开发了一个可靠的模型，并创建了一个易于使用的给药方案表，以指导临床医生进行VPA药物给药。
