有限采样法估算HSCT预处理患者白消安的暴露量

Limitied Sampling Strategy for Primary Estimation of the Area Under the Curve of Busulfan in HSCT Patients

目的探讨有限采样法（limited sampling strategy,LSS）估算异基因造血干细胞移植预处理患者白消安血药浓度药时曲线下面积AUC0-360 min的可行性。方法以17名患者静脉输注白消安为研究对象,在首剂和第9剂给药时,分别于给药前及给药后不同时间点采集血样,用高效液相色谱法测定血浆白消安浓度,采用多元线性回归选取1-4个采样点建立LSS模型,选取最佳模型估算药动学参数。结果以2-4个血药浓度数据预测药动学参数回归模型的线性关系较好,静脉输注白消安第1剂量2-4次采样最佳回归模型分别是240,300 min和180,240,360 min及120,150,180,240 min所建立的模型。第9剂量2-4次采样的最佳回归模型分别是120,240 min和15,135,180 min及120,240,300,360 min所建立的模型。结论 LSS法估算静脉输注白消安制剂的药动学参数是可行的,可用于白消安的临床血药浓度监测。

OBJECTIVE To estimate area under the curve between 0 and 6 h（AUC0-360 min） of busulfan in HSCT patients by limited sampling strategy（LSS）. METHODS All of 17 patients were given busulfan by intravenous infusion. At the first agent and the ninth agent, blood samples at different time points before and after drug administration were collected. The blood concentrations of busulfan were determined by a validated HPLC method. The 1-4 sampling points were selected to build limited sampling model, then chose the best model to estimate pharmacokinetic parameters. RESULTS The linear relationship of the model established by 2-4 drug concentration points was ideal. The best regression models of the intravenous infusion first dose were 180, 300 min; 180, 240, 360 min and 120, 150, 180, 240 min. Models of the ninth dose were 120, 240 min; 120, 150, 360 min and 120, 240, 300, 360 min. CONCLUSION To estimate pharmacokinetic parameters of busulfan by intravenous infusion in HSCT patients by limited sampling strategy is feasible. The method can applied in therapeutic drug monitoring.