肾功能不全患者人群中替考拉宁群体药代动力学模型的建立与验证

Population pharmacokinetics of teicoplanin in patients with renal insufficiency

目的:为了定量考察特殊人群病理、生理因素对替考拉宁体内过程的影响,本研究拟在肾功能不全患者人群中建立替考拉宁群体药代动力学模型,分析其用于预测替考拉宁血药浓度的可能性。方法:回顾性分析46例肾功能不全患者的66个常规血药浓度监测数据,采用Monolix 2021R1软件以非线性混合效应模型进行群体分析,建立替考拉宁单房室群体药代动力学模型。此外,收集20例肾功能不全患者的20个常规血药浓度监测数据,通过拟合优度参数法进行模型的外部验证。结果:静脉给药的一房室模型可以较好地描述肾功能不全患者人群中替考拉宁的药物代谢动力学特征,替考拉宁表观分布容积的群体典型值为148.9 L,清除率群体典型值为0.13 L/h,肾小球滤过率及体质量为影响替考拉宁体内消除的主要协变量,合并使用利尿剂等其他变量均未对替考拉宁的体内清除产生影响。结论:本研究建立的替考拉宁群体药代动力学模型稳健有效、具有良好的预测性能,可为肾功能不全患者的替考拉宁合理用药提供参考。

AIM:To analyze the effect of influential factors on the estimation of pharmacokinetic parameters of teicoplanin,this study was proposed to develop the population pharmacokinetic(PPK)model of teicoplanin in patients with renal insufficiency.METHODS:A total of 66 routine blood teicoplanin concentration monitoring data were collected from 46 cases with renal insufficiency,and a nonlinear mixed effect modeling program was used to establish one-compartment model with Monolix 2021R1 software.Furthermore,20 routine blood teicoplanin concentration monitoring data were also collected from the other 20 cases with renal insufficiency,and the external validation of the model was performed by goodness-of-fit parameter method.RESULTS:The one compartment model was an appropriate model for simulating the pharmacokinetics of teicoplanin in patients with renal insufficiency.The typical values of apparent volume of distribution and clearance rate were 148.9 L and 0.13 L/h,respectively.Glomerular filtration rate and body weight,instead of other factors,were the primary variables that affected the elimination of teicoplanin in vivo.CONCLUSION:The population pharmacokinetic model of teicoplanin established in the present study was effective and stable,which could also predict the dynamic change of teicoplanin concentration.As a result,the population pharmacokinetic model could provide references for the rational use of teicoplanin in special populations.