拉氧头孢钠在新生儿人群中群体药代动力学的分析研究  

Analysis of population pharmacokinetic models of Latamoxef in neonatal

作　　者：寇晨[1,2] 赵维[3,4] 肖婧[1] 申阿东[1] 

机构地区：[1]首都医科大学附属北京儿童医院北京市儿科研究所儿科学国家重点学科教育部儿科重大疾病研究重点实验室国家呼吸系统疾病临床医学研究中心儿童呼吸道感染性疾病研究北京市重点实验室,北京100045 [2]首都医科大学附属北京妇产医院NICU,北京100026 [3]山东大学药学院,山东济南250100 [4]山东大学附属千佛山医院药事部,山东济南250100

出　　处：《中国医刊》2017年第4期66-71,共6页Chinese Journal of Medicine

摘　　要：目的应用非线性混合效应模型(nonlinear mixed effect modeling,NONMEM)法,在新生儿人群中建立拉氧头孢钠群体药代动力学(pharmacokinetic,PPK)模型,为制定个体化给药方案提供参考。方法收集42例北京妇产医院新生儿重症监护病房应用拉氧头孢钠治疗感染的新生儿临床资料,包括生物学资料、用药资料、血药浓度测定结果及同期生化指标,其中采集有效血药浓度数据共64份。应用NONMEM软件,采用一级吸收和消除的一室模型,建立拉氧头孢钠在新生儿中的PPK模型。考察患儿的生物学信息以及同期生化指标对清除率(clearance,CL)和表观分布容积(volume of distribution,V)的影响。采用1000次自举法(Bootstrap)及正态预测分布误差(normalized predictive distribution error,NPDE)对模型进行验证。结果拉氧头孢钠在新生儿人群中的最终模型为:CL(L)=0.35×(纠正胎龄/38)^(2.51)×(每日体重/2390)^(0.75),V(L)=1.43×(每日体重/2390)。Bootstrap及NPDE结果与模型拟合值相符,具有更高的准确性和精确性。结论应用NONMEM软件成功地建立了新生儿阶段拉氧头孢钠的PPK模型,其中每日体重与纠正胎龄为影响清除率最重要的因素,每日体重为影响分布容积最重要的因素。Objective To establish population pharmaeokinetic （PPK） models of Latamoxef in neonatal by nonlinear mixed effect modeling （NONMEM）, and provide evidence for individualized drug therapy. Method Cases of 42 neonatal were collected from neonatal intensive care unit （NICU） in Beijing Obstetrics and Genecology Hospital. The clinical information included demography, medication, concentration data and blood biochemical parameters. A total of 64 concentration samples were extracted. Population pharmacokinetic model of Latamoxef was established by NONMEM program, using first-order absorption and elimination. Demography and blood biochemical parameter was investigated for influence on apparent clearance （CL） and apparent volume of distribution （V）. The reliability and stability of the PPK model was evaluated by 1000 times of Bootstrap procedure and normalized predictive distribution error （NPDE）. Result The final model of Latamoxef in neonatal： CL （L/h）=0.35 ~ （postmenstrual/38）251 ~ （current weight/2390）~75, V（L）=l.43 ~ （current weight/2390）. The results of Bootstrap and NPDE procedure are corresponding to the estimates from NONMEM. Conclusion PPK models of Latamoxef in neonatal were successfully established. Current weight and postmenstrual age were identified as a significant covariate on Latamoxef apparent clearance. Current weight was identified as a significant covariate on Latamoxef apparent volume of distribution.

关 键 词：拉氧头孢钠 群体药代动力学 新生儿 

分 类 号：R917[医药卫生—药物分析学]