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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。
Objective To investigate the pharmacokinetic characteristics of allo-HSCT adult patients after intravenous infusion of high-dose busulfan pretreatment and its correlation with clinical efficacy and toxicity. Methods 34 adult patients with allogeneic hematopoietic stem cell transplantation were treated with busulfan 1.6 mg · kg-1, q12 h for 8 consecutive days. When the first dose and the fifth and seventh dose were administered, blood samples were taken before administration and at different time points after administration, respectively, and the concentration of busulfan was determined by liquid chromatography-tandem mass spectrometry. The non-compartment method Pharmacokinetic parameters were calculated. Results The first and seventh dose of Baixianan in allogeneic hematopoietic stem cell transplantation in patients with metabolic processes consistent with one-compartment model, the main pharmacokinetic parameters were: 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) and (2.2 ± 0.7) μmol·L- The AUC and cav values increased after the seventh dose administration (P <0.05). Patient clearance was negatively correlated with body weight (P <0.05). Conclusion Metabolic process of intravenous busulfan in adult patients with allogeneic hematopoietic stem cell transplantation is consistent with one-compartment pharmacokinetic model. There is a great difference among individuals, and the clearance rate is negatively correlated with body weight. Monitoring the therapeutic drugs is beneficial to the clinical treatment of patients.