rhG-CSF治疗儿童ALL的药效学及药代动力学分析

Pharmacodynamics and Pharmacokinetics of recombinant human granulocyte colony stimulating factor in children with acute lymphoblastic leukemia

目的探究重组人粒细胞集落刺激因子(rhG-CSF)治疗儿童急性淋巴细胞白血病(ALL)的药效学及药代动力学特征。方法选择126例ALL患儿相关资料进行回顾性分析,所有患者均接受柔红霉素+阿糖胞苷+依托泊苷(DAE)化疗,根据患者治疗期间是否应用rhG-CSF将患儿分为研究组38例和对照组88例,比较两组患者治疗疗效以及安全性,分析rhG-CSF药动力学情况。结果研究组患者疾病控制率、中性粒细胞绝对值(ANC)最低值高于对照组,粒细胞减少时间、粒细胞缺乏时间、粒缺伴发热时间低于对照组;研究组患者胃肠道感染、肺炎、败血症发生率低于对照组;研究组骨髓抑制不良反应发生率低于对照组(P<0.05)。rhG-CSF血药质量浓度随着rhG-CSF注入时间先上升后下降,ANC水平低时,rhG-CSF清除速度缓慢,ANC上升至正常水平时,rhG-CSF清除速度上升;药代动力学参数药峰浓度、总清除率、消除半衰期、达峰时间、平均滞留时间中位数分别为356.24μg/L、3.13 mL/(h·kg)、15.24 h、48.00 h、79.53 h。结论儿童ALL采用rhG-CSF治疗疗效与安全性优异,药代动力学特点与中性粒细胞介导清除机制相符。

Aim To explore the pharmacodynamics,pharmacokinetics and safety of recombinant human granulocyte colony stimulating factor(rhG-CSF)in children with acute lymphoblastic leukemia(ALL).Methods A retrospective analysis was performed on the relevant data of 126 children with ALL.All of them underwent DAE chemotherapy.According to presence or absence of rhG-CSF during treatment,they were divided into study group(n=38)and control group(n=88).The curative effect and safety between the two groups were compared.The pharmacokinetics of rhG-CSF was analyzed.Results The disease control rate and ANC minimum in study group were significantly higher than those in control group,and neutropenia time,agranulocytosis time and duration of agranulocytosis combined with fever were significantly shorter than those in control group.The incidence of gastrointestinal trac,pneumonia and sepsis in study group were significantly lower than those in control group(P<0.05).The incidence of myelosuppression in study group was significantly lower than that in control group(P<0.05).The plasma concentration of rhG-CSF was increased first and then decreased with the injection time of rhG-CSF.When ANC level was low,clearance rate of rhG-CSF was slow.When ANC level returned to normal,clearance rate of rhG-CSF was increased.The median values of peak concentration of drug,total clearance rate,elimination half-life,time to peak and mean detention time were 356.24μg/L,3.13 mL/(h·kg),15.24 h,48.00 h and 79.53 h,respectively.Conclusion The curative effect and safety of recombinant human granulocyte colony stimulating factor are excellent in ALL children.The pharmacokinetics characteristics are consistent with neutrophil-mediated clearance mechanism.