儿童肾功能评估公式和更昔洛韦清除率的相关性确证与剂量优化

目的:采用群体药动学分析方法考察不同肾小球滤过率(GFR)公式估计更昔洛韦清除率的适用性,并用于更昔洛韦给药剂量优化。方法:收集100例患者的血药浓度数据和临床资料,采用基于不同生物标志物的公式计算GFR。建立儿童患者静脉滴注更昔洛韦的群体药动学模型,考察体质量和肾功能对药动学参数的影响,并对最终模型进行内部验证。在建模过程中探索不同公式获取的GFR和更昔洛韦清除率之间的相关性。确定最适用的GFR公式后,根据体质量和肾功能对给药剂量进行个体化设计。结果:具有一级消除的一房室模型能够很好地描述更昔洛韦在儿童群体中的药动学特征。验证结果显示最终模型稳定可靠,预测性能较好。综合可视化检验和协变量分析结果,可确定Flanders Metadata公式计算获得的GFR与更昔洛韦清除率相关性较高,临床适用性较好。在此基础上提出了基于GFR和患者体质量的个体化给药方案。结论:本研究确证了最适用于预测儿童群体更昔洛韦清除率的GFR公式,为该药物治疗提供了一种基于建模手段的个体化给药策略。

Confirmation of the association between renal function assessment formula for children and ganciclovir clearance and dose optimization

OBJECTIVE To evaluate the applicability of different glomerular filtration rate (GFR) formulas for estimating ganciclovir clearance using a population pharmacokinetic approach and to optimize the dosage regimens.METHODS Serum concentrations and clinical data from 100 patients were collected and GFR was calculated by formulas based on different biomarkers.A population pharmacokinetic model of ganciclovir intravenous in pediatric patients was developed to investigate the influence of body weight and renal function on pharmacokinetic parameters,and the final model was validated internally.Correlations between GFR and ganciclovir clearance obtained with different formulas were explored during the modeling process.After the most appropriate GFR formula was identified,the dosage regimens were designed according to body weight and renal function.RESULTS A one-compartment model with first-order elimination could well characterize the pharmacokinetic profile of ganciclovir in pediatric population.The validation results revealed the robustness and good predictive performance of the final model.Considering the results of visual inspection and covariate analysis,it was evident that the GFR obtained from the Flanders Metadata formula correlated well with ganciclovir clearance and was applicable to clinical practice.On this basis,individualized dosage regimens were proposed according to GFR and body weight of patients.CONCLUSION In the present study,the GFR formula which is most appropriate for the prediction of ganciclovir clearance in pediatric population is confirmed,and a model-based individualized dosing strategy for ganciclovir treatment is provided.