静脉输注白消安在异基因造血干细胞移植预处理患者体内的药动学研究

 目的 研究异基因造血干细胞移植（allo-HSCT）预处理患者静脉输注大剂量白消安的药动学特征。方法 17例allo-HSCT预处理患者静脉输注白消安0.8 mg·kg^-1，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剂静脉滴注给药后白消安在allo-HSCT预处理患者体内过程均符合二室模型，其主要药动学参数分别为：CL（0.004 2±0.001 8）与（0.002 8±0.001 3）L·min^-1·kg^-1、AUC_0-t（612.3±182.8）与（1 005.4±286.2）μmol·min·L^-1、AUC_0-∞ （899.5±298.6）与（1 484.4±623.0）μmol·min·L^-1；ρ_max（2.95±0.81）与（4.53±1.42）μmol·L^-1。不同性别患者的主要药动学参数有显著差异。结论 静脉滴注白消安在allo-HSCT预处理患者体内过程符合二室药动学模型，主要药动学参数个体差异大且与性别有关，开展治疗药物监测仍有必要。

Pharmacokinetics of Intravenous Busulfan in Patients Prior to Allogeneic Hematopoietic Stem Cell Transplantation

OBJECTIVE To study the pharmacokinetic profiles of intravenous busulfan in Chinese patients undergoing allogeneic hematopoietic stem cell transplantation. METHODS Blood samples of 17 adult patients were collected following the first and the ninth dose of a standard 16 dose intravenous busulfan，4-day regimen. The plasma concentrations 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 intravenous busulfan of 0.8 mg·kg-1 in 17 patients were fit to a two-compartment model，respectively. The main pharmacokinetic parameters were as followCL （0.004 2±0.001 8） and （0.002 8±0.001 3）L·min-1·kg-1， AUC_0-t（612.3±182.8） and （1 005.4±286.2） μmol·min·L-1， AUC_0-∞ （899.5±298.6） and （1 484.4±623.0） μmol·min·L-1， ρ_max（2.95±0.81） and （4.53±1.42）μmol·L-1， respectively. The main pharmacokinetic parameters after intravenous administration of busulfan 0.8 mg·kg-1 were different between female and male. CONCLUSION The pharmacokinetic profiles of intravenous busulfan are fit to two-compartment model，the inter- and intrapatient variability in the main pharmacokinetic parameters（such as CL, AUC_0-t, AUC_0-∞ and ρ_max are significant statistically and related to gender. Intravenous busulfan pharmacokinetics should need more research and the therapeutic monitoring and appropriate dose adjustment may be recommended.