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

苏汉中, 张善堂, 孙自敏, 唐丽琴, 方焱, 刘会兰, 邱蕾, 童彤, 疏义杰, 崔文军, 王春梅

中国药学杂志 ›› 2016, Vol. 51 ›› Issue (21) : 1860-1865.

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中国药学杂志 ›› 2016, Vol. 51 ›› Issue (21) : 1860-1865. DOI: 10.11669/cpj.2016.21.007
论著

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

  • 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3, 崔文军3, 王春梅3
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Population Pharmacokinetics of Intravenous Infusing Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation

  • SU Han-zhong1,2,3, ZHANG Shan-tang1*, SUN Zi-min1, TANG Li-qin1, FANG Yan1, LIU Hui-lan1, QIU Lei1,2, TONG Tong1, SHU Yi-jie3, CUI Wen-jun3, WANG Chun-mei3
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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。

Abstract

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.

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

Key words

busulfan / allogeneic hematopoietic stem cell transplantation / population pharmacokinetics / NONMEM / individualised dosing regimen

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苏汉中, 张善堂, 孙自敏, 唐丽琴, 方焱, 刘会兰, 邱蕾, 童彤, 疏义杰, 崔文军, 王春梅. 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[J]. 中国药学杂志, 2016, 51(21): 1860-1865 https://doi.org/10.11669/cpj.2016.21.007
SU Han-zhong, ZHANG Shan-tang, SUN Zi-min, TANG Li-qin, FANG Yan, LIU Hui-lan, QIU Lei, TONG Tong, SHU Yi-jie, CUI Wen-jun, WANG Chun-mei. Population Pharmacokinetics of Intravenous Infusing Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation[J]. Chinese Pharmaceutical Journal, 2016, 51(21): 1860-1865 https://doi.org/10.11669/cpj.2016.21.007
中图分类号: R969.1   

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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)
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