儿科肾病综合征患者他克莫司群体药代动力学模型的外部验证

External evaluation of published population pharmacokinetic models of tacrolimus in pediatric patients with nephrotic syndrome

目的验证国内外现有他克莫司群体药代动力学模型对中国肾病综合征儿科患者血药浓度数据的拟合效果。方法本研究通过检索Pub Med和中国知网等数据库,分析了已发表的关于他克莫司的群体药代动力学模型,并提取了文献中的模型信息。收集我院2011年至2017年使用他克莫司治疗肾病综合征的患儿的人口学信息、给药方案和治疗药物监测(TDM)信息。根据整理得到的模型信息对我院肾病综合征患儿的血药浓度数据进行拟合。根据拟合优度图(GOF图)及可视化预测检验(VPC)评估拟合效果。结果本研究共纳入我院41例肾病综合征患儿的96个稳态谷浓度点,入组患儿年龄范围为1. 70～15. 20岁;共纳入6篇他克莫司的群体模型进行拟合,拟合效果均较差。结论现有的他克莫司群体药代动力学模型对我国儿科肾病综合征患者血药浓度预测性能较差,仍需建立适合我国儿科肾病综合征患者的群体药代动力学模型。

Objective To analyze the published population pharmacokinetic models of tacrolimus in order to investigate the applicability of these models in different clinical settings,and to select the potential appropriate models for Chinese pediatric patients. Methods We searched PubMed,CNKI and other databases to analyze published models of tacrolimus,extracted model information. We collected demographic information,dose regimen and therapeutic drug monitoring( TDM) information from pediatric patients in our hospital between 2011 and 2017. And we applied the models into these patients to evaluate the capacity of prediction. The accuracy of prediction of these models was evaluated based on Goodness of Fit graph( GOF graph) and Visual Predicted Checks( VPC). Results We recorded 96 whole blood concentrations of tacrolimus from 41 patients aging from 1. 70 to 15. 20 years old. Six published models were included and simulated,none of which had a good capacity of prediction. Conclusion It is necessary to reestablish the population pharmacokinetic models of tacrolimus in pediatric patients with nephrotic syndrome.