新生早产儿万古霉素的群体药动学模型  

Population pharmacokinetic model of vancomycin in preterm neonates

作　　者：余晓霞[1] 管宴萍 王莹[1] 邱凯锋[1] 伍俊妍[1] YU Xiaoxia;GUAN Yanping;WANG Ying;QIU Kaifeng;WU Junyan(Department of Pharmacy,Sun Yat-sen Memorial Hospital,Guangzhou 510120,China)

机构地区：[1]中山大学孙逸仙纪念医院药学部,广州510120

出　　处：《中国临床药学杂志》2022年第5期346-351,共6页Chinese Journal of Clinical Pharmacy

基　　金：广东省医院药学研究基金(编号2021A42)

摘　　要：目的基于非线性混合效应方法建立新生早产儿万古霉素的群体药动学模型,促进个体化用药。方法回顾性收集170例新生早产儿静脉注射万古霉素(40~60 mg·kg^(-1)·d^(-1))后的275个稳态谷浓度数据及对应的临床信息,建立新生早产儿万古霉素的药动学模型。采用逐步回归法筛选可能影响的协变量,通过统计学相关参数及诊断图形对模型进行拟合优度的评价,并采用自举法和可视化方法验证最终模型的准确性和稳定性。结果结合异速生长和成熟度公式的一房室模型可较好地拟合万古霉素在新生早产儿体内的过程,表观分布容积和清除率的群体典型值分别为48.0 L·(70 kg)^(-1),0.393 L·(70 kg)^(-1)·h^(-1);体质量、矫正胎龄以及肾功能对清除率具有显著性影响;拟合优度、可视化验证及自举法结果表明,模型稳健,参数估算及预测结果可靠。结论该研究建立的万古霉素群体药动学模型在新生早产儿群体中具有较好的稳定性与可靠的预测效能,可为临床新生早产儿的临床个体化精准用药提供科学依据。AIM To establish a population pharmacokinetic model of vancomycin in preterm neonates and promote individualization of medication.METHODS Totally of 170 preterm neonates were admitted and 275 plasma trough concentrations at steady state were collected after administration vancomycin intravenously(40-60 mg·kg^(-1)·d^(-1)).The concentrations were utilized to set up a population pharmacokinetic model and covariates related to weight and maturation of organ were collected.Stepwise method was applied to analysis the significant covariates.The outputs were evaluated by the statistic parameters and diagnostic plots.The final model was validated using a bootstrap and visual predictive check.RESULTS The pharmacokinetic data of vancomycin in preterm neonates were well described by a one-compartment model that incorporated allometric scaling method and maturation model.The estimated clearance and apparent distribution volume were 0.393 L·(70 kg)^(-1)·h^(-1)and 48.0 L·(70 kg)^(-1),respectively.Weight,postmenstrual age and renal function had significant influence on the clearance of vancomycin.The results of goodness of fit plots,visual predictive check and bootstrap illustrated that the established model was robust and the parameter estimation and prediction results were reliable.CONCLUSION The population pharmacokinetic model of vancomycin in preterm neonates has good stability and reliable prediction efficiency.It can provide scientific basis for clinical individualized and precise medication of preterm neonates.

关 键 词：早产儿 万古霉素 群体药动学 异速生长 

分 类 号：R969.1[医药卫生—药理学]