白消安在造血干细胞移植患者体内的药动学特征

Pharmacokinetic profiles of intravenous busulfan in hematopoietic stem cell transplantation patients

目的评价白消安在异基因造血干细胞移植(HSCT)患者体内的药动学特征。方法 24例HSCT患者于白消安预处理第1剂前0 h与第1剂后1、2、3、4、5和6 h采集血样,利用DAS 2.0软件进行房室模型拟合,计算药动学参数,并借助SPSS20.0软件分析药动学参数的影响因素。结果第1剂静脉输注白消安后在HSCT患者体内过程符合二室模型,白消安的AUC_(0→6h)与AUC_(0→∞)分别在524.71~946.91μmol·min·L^(-1)与754.96~1 787.42μmol·min·L^(-1)范围内波动,t_(1/2α)、t_(1/2β)、CL等参数变异性大。非慢性髓细胞性白血病组与慢性髓细胞性白血病组的c_(max)之间差异有统计学意义。结论 HSCT患者体内白消安药动学参数变异性较大,有必要进行治疗药物监测。

AIM To study the pharmacokinetic profiles of intravenous busulfan in patients undergoing allogeneic hematopoietic stem cell transplantation(HSCT).METHODS Blood samples were collected from 24 HSCT patients at specific time points,namely,0 h before the first dose of busulfan preparative regimen,1,2,3,4,5 and 6 h after the first dose.DAS 2.0 software was used to do the statistical analysis,determine the compartment model and calculate pharmacokinetic parameters.SPSS 20.0 software was used to examine the influence of factors on pharmacokinetic parameters of busulfan.RESULTS The plasma concentration-time curves after the first dose of intravenous busulfan in 24 patients were fitted to a two-compartment model.AUC_(0→6h) and AUC_(0→∞) of busulfan in HSCT patients varied in the range524.71-946.91 μmol·min·L^(-1) and 754.96- 1 787.42 μmol· min·L^(-1),respectively.t_(1/2α),t_(1/2β),CL had a large variability.This study found significant difference in c_(max) between non-CML group and CML group.CONCLUSION The variability of busulfan pharmacokinetic parameters in HSCT patients is significant.There is a need for therapeutic drug monitoring.