目的 研究异基因造血干细胞移植(allo-HSCT)成人患者静脉滴注大剂量白消安预处理后的药动学特征及与患者临床疗效和毒性反应的相关性。方法 34例异基因造血干细胞移植成人患者静脉滴注白消安1.6 mg·kg-1, q12 h, 连续8剂。在首剂和第 5、7剂给药时, 分别于给药前及给药后不同时间点采集血样, 用液相色谱-串联质谱法测定白消安浓度, 采用WinNonLin软件以非房室法计算药动学参数。结果 首剂和第 7 剂静脉滴注给药后白消安在异基因造血干细胞移植成人患者体内代谢过程符合一室模型, 主要药动学参数分别为:CL(4.1±1.8), (4.6±1.9) mL·min-1·kg-1;Vd(1.3±0.5), (1.2±0.5) L·kg-1;AUC0-12(1 218.5±351.0), (1 501.2±444.3) μmol·min· L-1;AUC0-∞(1 694.8±741.7), (1 882.2±754.1) μmol·min· L-1;cav(1.8±0.6), (2.2±0.7)μmol· L-1。第7剂给药后AUC及cav值较第1剂增加(P＜0.05)。患者清除率与其体重呈负相关(P＜0.05)。结论 异基因造血干细胞移植成人患者体内静脉滴注白消安的代谢过程符合一室药动学模型, 个体间差异较大, 清除率和体重负相关, 开展治疗药物监测有利于患者临床治疗。
Abstract
OBJECTIVE To study the pharmacokinetics of intravenous busulfan in Chinese adult patients undergoing allogeneic hematopoietic stem cell transplantation and its correlation with clinical outcome. METHODS Blood specimens of 34 patients were collected following the first, fifth and seventh dose of an intravenous administration of busulfan at 1.6 mg·kg-1 every 12 hours for 4 days. The concentrations of busulfan in blood plasma were determined by LC-MS.The pharmacokinetic parameters were calculated according to non-compartment model by WinNoLin statistical software. RESULTS The pharmacokinetics behavior after dose 1 and dose 7 of intravenous busulfan in 34 patients were all fit to a one compartment model. The main pharmacokinetic parameters were as follow:CL(4.1±1.8), (4.6±1.9) mL·min-1·kg-1;Vd(1.3±0.5), (1.2±0.5) L·kg-1;AUC0-12(1 218.5±351.0), (1 501.2±444.3) μmol·min·L-1;AUC0-∞(1 694.8±741.7), (1 882.2±754.1) μmol·min· L-1;cav(1.8±0.6), (2.2±0.7) μmol· L-1.AUC and cav of dose 7 were higher than dose 1(P＜0.05). The patient′s body weight negatively correlated with CL(P＜0.05). CONCLUSION The pharmacokinetics profiles of twice-daily intravenous busulfan are fit to a one compartment model.The pharmacokinetics of busulfan varied in different doses and patients. Therapeutic drug monitoring(TDM) of busulfan will be important to clinical treatment.
关键词
白消安 /
静脉滴注 /
异基因造血干细胞移植 /
药动学
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Key words
busulfan /
intravenous /
allogeneic hematopoietic stem cell transplantation /
pharmacokinetics
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中图分类号：
R969.1
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参考文献
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