目的 建立有限采样方法(limited sampling strategy, LSS)用于估算造血干细胞移植(hematopoietic stem cell transplantation,HSCT)患者静脉滴注白消安(busulfan,Bu)后的药-时曲线面积(an area under the plasma concentration versus time curve,AUC)。方法 22例造血干细胞移植患者静脉滴注白消安后,采集若干时间点血浆样品,用LC-MS/MS测定白消安血药浓度,用经典方法计算药动学参数。另以稀疏血药浓度数据点建立多元回归数学模型,估算AUC0-6,并对模型进行验证。通过组内相关系数(intraclass correlation coefficient,ICC)和Bland-Altman (BA)分析评估经典法和有限采样方法的一致性。结果 两点(C2、C5)预测的药动学参数回归模型的线性关系较好(调整的r2=0.917),平均预测误差为0.20%,均方根误差为4.48%,组内相关系数的95%置信区间为0.914~0.984,BA分析一致性界限为-0.9~8.8。与经典法评价结果一致。结论 C2、C5估算AUC0-6的有限采样法可用于白消安的临床血药浓度监测。
Abstract
OBJECTIVE To establish limited sampling strategy to estimate area under the curve (AUC) of HSCT patients who had received busulfan (Bu) intravenous infusion. METHODS Plasma samples were collected at certain time points from 22 HSCT patients who had received busulfan intravenous infusion. The LC-MS/MS method was used to measure blood concentration of busulfan. The classical method was used to calculate pharmacokinetic parameters. To estimate AUC0-6, measured blood concentration data was used to build a multiple linear regression model which was subsequently validated. Consistency between results produced by the traditional method and the proposed LSS respectively was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) analysis. RESULTS It is shown that model based on concentrations on two sampling time points (2 and 5 h) is able to predict AUC0-6accurately (adjusted r2=0.917. MPE=0.2%, RMSE=4.48%). The 95% confidence interval of ICC is 0.914-0.984 while the limit of agreement in the BA is -0.9-8.8. Results produced by limited sampling strategy are nearly consistent with AUC0-6 produced by the classical method. CONCLUSION The proposed limited sampling strategy to estimate AUC0-6 based on C2 and C5 can be used to busulfan blood concentration monitoring in clinical practice.
关键词
白消安 /
经典法 /
有限采样法 /
血药浓度监测
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Key words
classic method /
limited sampling strategy /
blood concentration monitoring
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中图分类号：
R969.1
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参考文献
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脚注
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基金
福建省战略新兴技术应用资助项目(2013J01371);福建省教育厅科研资助项目(JB11058)
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