万古霉素在新生儿和小婴儿患者中的群体药动学研究

发布时间：2018-10-10 16:32

【摘要】：目的建立万古霉素在新生儿和小婴儿患者的群体药动学(PPK)模型,为临床个体化用药提供参考。方法收集85例新生儿科患者静脉注射使用万古霉素后的血药浓度数据和临床资料。将患者分为两组,模型组(n=71)采用Phoenix~汶NLME~(TM)1.3软件进行PPK分析,建立一房室药动学模型(个体间变异采用指数模型,个体内变异采用混合误差模型),考察各协变量对参数V和CL的影响。用拟合优度、自举法对最终模型的性能进行内部验证。采用验证组(n=14)患者的血药浓度,计算平均预测误差(MPE)、平均绝对预测误差(MAE)、平均预测误差均方(MSPE)对最终模型进行外部验证。结果 PPK最终模型为V(L)=3.167,CL(L·h~(-1))=0.413×(WT/3.32)~(0.747)×(PNA/25)~(0.402)×e~(ηCL),体重(WT)和产后日龄(PNA)对CL有影响。拟合优度、自举验证的结果表明最终模型稳定、预测结果可靠。外部验证最终模型计算MPE、MAE和MSPE值分别为(-0.843±1.347)、(1.462±1.175)和(2.432±4.293)mg·L~(-1)。血药浓度实测值和最终模型的个体预测值的决定系数R=0.955,外部验证说明最终模型预测准确度较好。结论本研究建立的万古霉素新生儿和小婴儿患者的PPK模型预测能力和稳定性良好,可为其个体化给药方案的制订提供参考。
[Abstract]:Objective to establish a group pharmacokinetic (PPK) model of vancomycin in neonates and infants. Methods the blood concentration data and clinical data of 85 cases of pediatric patients received vancomycin intravenously were collected. The patients were divided into two groups. The model group (NQ71) was analyzed by PPK using Phoenix~ Wen NLME~ (TM) 1.3 software, and an atrioventricular pharmacokinetic model was established. The effects of covariables on parameters V and CL were investigated by using a mixed error model. The performance of the final model is verified by self-booting method and goodness of fit. The mean prediction error (MPE), mean absolute prediction error (MAE), mean square (MSPE) (MSE) were used to verify the final model. Results the final model of PPK was V (L) = 3.167 L (L h-1) = 0.413 脳 (WT/3.32) ~ (0.747) 脳 (PNA/25) ~ (0.402) 脳 E ~ (畏) (WT) and (PNA) of postpartum day had influence on CL. The results of goodness of fit and bootstrap verification show that the final model is stable and the prediction result is reliable. The calculated values of MPE,MAE and MSPE were (- 0.843 卤1.347), (1.462 卤1.175) and (2.432 卤4.293) mg L ~ (-1), respectively. The determinant coefficient of the blood drug concentration and the individual predictive value of the final model was 0.955. The external verification showed that the prediction accuracy of the final model was better than that of the final model. Conclusion the predictive ability and stability of vancomycin PPK model for neonates and infants with vancomycin are good, which can be used as reference for the formulation of individualized administration of vancomycin.
【作者单位】：重庆医科大学附属儿童医院药学部儿童发育疾病研究教育部重点实验室儿童发育重大疾病国家国际科技合作基地;重庆医科大学附属儿童医院信息科儿科学重庆市重点实验室;
【基金】：重庆市教育委员会科学技术研究项目(KJ1702038)
【分类号】：R969.1

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