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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。
OBJECTIVE: To establish a limited sampling strategy (LSS) for the estimation of the drug-time area of intravenous infusion of busulfan (Bu) in patients with hematopoietic stem cell transplantation (HSCT) plasma concentration versus time curve, AUC). Methods Twenty-two patients with hematopoietic stem cell transplantation were treated with busulfan, and plasma samples were collected at several time points. The plasma concentration of busulfan was determined by LC-MS / MS. Pharmacokinetic parameters were calculated by classical methods. Another sparse blood drug concentration points to establish multiple regression mathematical model, estimate AUC0-6, and verify the model. The agreement between classical and finite sampling methods was evaluated by intraclass correlation coefficient (ICC) and Bland-Altman (BA) analysis. Results The linear regression model of two pharmacokinetic parameters (C2 and C5) predicted good linearity (adjusted r2 = 0.917), the average prediction error was 0.20%, the root mean square error was 4.48%, and the correlation coefficient of group 95 % Confidence interval was 0.914 ~ 0.984, BA analysis consistency limit was -0.9 ~ 8.8. Consistent with the results of the classic method. Conclusions C2, C5 The AUC0-6 limited sampling method can be used to monitor the clinical plasma concentration of busulfan.