造血干细胞移植预处理患者静脉输注白消安的群体药动学研究  

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

作　　者：苏汉中[1,2,3] 张善堂[1] 孙自敏[1] 唐丽琴[1] 方焱[1] 刘会兰[1] 邱蕾[1,2] 童彤[1] 疏义杰 崔文军 王春梅 

机构地区：[1]安徽省立医院,合肥230001 [2]安徽中医药大学药学院,合肥230031 [3]安徽天星医药集团有限公司,合肥230031

出　　处：《中国药学杂志》2016年第21期1860-1865,共6页Chinese Pharmaceutical Journal

基　　金：安徽省2015年公益性技术应用研究联动计划资助项目(1501ld04026)

摘　　要：目的建立异基因造血干细胞移植患者静脉输注白消安的群体药动学模型,考察白消安药动学参数的影响因素。方法收集35名行造血干细胞移植术并采用白消安药物治疗的患者相关生理病理信息及药物浓度数据,运用非线性混合效应模型进行群体药动学数据分析。结果建立了包含患者个体间变异、个体内变异及体重、性别、血肌酐清除率等变量的统计学模型。自举法运行1 000次,成功973次,与NONMEM最终模型原计算结果比较,各项参数的估算值均较接近原值,最终模型具有较好的精密度、准确性及稳定性。结论建立的群体药动学模型能较好的描述患者药动学特点,患者体重和性别及血肌酐清除率对药动学参数有影响。可为临床制定个体化给药治疗方案提供参考。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 infor- mation such as physiological and pathological factors and busulfan concentration data were used to perform the population pharmacoki- netic 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 resam- piing 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 pharmacokinetie model of busulfanis stable, effective and predictable. CONCLUSION The population pharmacokinetic model is established,which is capable of depicting the pharmacokinetic characteris- tics 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.

关 键 词：白消安 异基因造血干细胞移植 群体药动学 非线性混合效应模型 个体化给药 

分 类 号：R969.1[医药卫生—药理学]