Pharmacokinetics of intravenous busulfan in adult patients undergoing allogeneic hematopoietic stem cell transplantation / 中国药学杂志

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 (1218.5±351.0), (1501.2±444.3)μmol·min·L-1; AUC0-∞ (1694.8±741.7), (1882.2±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.