白消安在重型地中海贫血患儿中的群体药代动力学研究

Research on population pharmacokinetics of busulfan in pediatric patients with thalassemia major

目的建立白消安在重型地中海贫血患儿中的群体药代动力学模型,为此类患儿白消安的个体化给药提供依据。方法收集静脉使用白消安的儿童地中海贫血患者306名共2142个血样,用LC-MS/MS测定白消安血药浓度,详细记录相关临床数据。使用Monolix软件建立白消安的群体药代动力学模型。结果静脉给药一室模型能很好地描述白消安的药代动力学特征,白消安的表观分布容积(V)、清除率(CL)的群体典型值分别为12.10 L,3.83 L·h^-1。体表面积和肌酐清除率对模型有显著影响。结论本研究成功建立的白消安群体药代动力学预测性能稳定良好,可为临床白消安的个体化给药提供参考。

Objective To establish a population pharmacokinetic model of busulfan in pediatric patients with thalassemia major and provide a basis for personalizing administration of busulfan.Methods 2142 blood samples from 306 pediatric patients were collected.LC-MS/MS method was used to determine the plasma concentrations of busulfan.The population pharmacokinetic model of busulfan was established using Monolix software.Results A one compartment model fits best.The structural model value of distribution volume is 12.10 L,and the clearance rate is 3.83 L·h^-1.The covariates are body surface area and creatinine clearance.Conclusions This study has established the PPK model of busulfan in pediatric patients with thalassemia major,which was reliable and has good predictive performance.It’s suitable to provide a basis for clinical practice.