大剂量口服白消安在异基因造血干细胞移植处理患者体内的药代动力学研.docVIP

大剂量口服白消安在异基因造血干细胞移植预处理患者体内的药代动力学研究 摘要：目的 研究口服大剂量白消安在异基因造血干细胞移植（allo-HSCT）预处理患者体内的药代动力学特征。方法 allo-HSCT预处理患者口服白消安1mg/kg，q6h，共16剂。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；用DAS软件进行药动学房室模型拟合，计算药动学参数。结果 首剂和第9剂给药后白消安在allo-HSCT预处理患者体内血药浓度-时间曲线均符合一室模型，其主要药动学参数分别为：t1/2 （133.03±30.62）与（131.39±28.15）min、Ke （0.005±0.001）与（0.006±0.001）min-1、Vd/F（0.562±0.119）与（0.459±0.077）L/kg、CL/F（0.003±0.001）与（0.003±0.001）L/min/kg、AUC(0-t)（910.3±146.9）与（1158.5±139.0）μmol/L*min、AUC(0-∞) （1401.9±243.2）与（1689.0±312.4）μmol/L*min；白消安平均稳态血浆浓度为（3.29±0.39）μmol/L。结论 口服大剂量白消安在allo-HSCT预处理患者体内过程符合一室药动学模型，主要药动学参数个体差异大，多次给药后药物清除率发生改变。 关键词：白消安；异基因造血干细胞移植；预处理方案；药代动力学 Pharmacokinetics of oral busulfan in patients undergoing allogeneic hematopoietic stem cell transplantation ABSTRACT OBJECTIVE To study the pharmacokinetic profiles of oral busulfan in Chinese patients undergoing allogeneic hematopoietic stem cell transplantation. METHODS Blood samples of 9 adult patients were collected following the first and the ninth dose of a standard 16 dose oral busulfan，4-day regimen. The plasma concentration of busulfan were determined by HPLC, and the pharmacokinetic parameters of busulfan were calculated by DAS statistical softwere. RESULTS The plasma concentration- time curves after dose 1 and dose 9 oral busulfan 1mg/kg in 9 patients were fit to one-compartment model，respectively；The main pharmacokinetic parameters were as follow：t1/2 （133.03±30.62）and（131.39±28.15）min、Ke（ 0.005±0.001）and（0.006±0.001）min-1、Vd/F（0.562±0.119）and（0.459±0.077）L/kg、CL/F（0.003±0.001）and（0.003±0.001）L/min/kg、AUC(0-t)（910.3±146.9）and（1158.5±139.0）μmol/L*min、AUC(0-∞)（1401.9±243.2）and（1689.0±312.4）μmol/L*min，respectively. Busulfan average steady plasma concentration were （3.29±0.39）μmol/L. CONCLUSION The pharmacokinetic profiles of oral busulfan are fit to one-compartment model ，and the main pharmacokinetic parameters（ such as Vd/F、CL/F AUC(0-t)、AUC(0-∞)）are significant difference between dose 1 and dose 9. KEY WORDS： busulfan；all