Population Pharmacokinetics of Intravenous Infusing Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation

OBJECTIVE To establish a population pharmacokinetic model of intravenous infusing busulfan in HSCT patients,and to explore physiological and pathological factors which may influence the pharmacokinetic parameters. METHODS We have collected clinical history information of 35 patients undergoing HSCT surgery and taking busulfan intravenous infusion for treatment. These information such as physiological and pathological factors and busulfan concentration data were used to perform the population pharmacokinetic analysis by applying the method of nonlinear mixed effects modeling( NONMEM). RESULTS A statistical model of busulfan is established,including variables such as body weight,sex,serum creatinine clearance. The success of 973 out of 1 000 times resampling trials( by bootstrap) shows that the newly parameters value are very close to the estimate value calculated from the final model by NONMEM,which demonstrates the established population pharmacokinetic model of busulfanis stable,effective and predictable.CONCLUSION The population pharmacokinetic model is established,which is capable of depicting the pharmacokinetic characteristics of busulfan. It is found that patients’ weight,gender and creatinine clearance influence pharmacokinetic parameters,which can be useful and valuable for the clinical individualized dosing regimens.