Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients
Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients
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DOI：
10.3390/pharmaceutics11060259
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发表时间：
2019-06-01
期刊：
影响因子：
5.4
通讯作者：
Yun, Hwi-yeol
中科院分区：
文献类型：
--
作者：
Back, Hyun-moon;Lee, Jong Bong;Yun, Hwi-yeol
传统上，儿科患者的剂量是通过简单的称重方法进行优化的，但这些方法并不总是满足儿童的要求。为了克服这种差异，人们提出了大小和成熟函数的群体药代动力学(PK)模型。本研究的主要目的是使用来自三个不同临床研究的临床数据来评估一种新的儿科患者建模方法。为了建立PK模型，采用了一种非线性混合效应建模方法，并用异速生长的大小和Michaelis-Menten型函数的成熟度来探讨儿童PK的差异。模型评价采用拟合度图、视觉预测检验和Bootstrap方法。对于一岁以上的儿童来说，单一应用大小比例来衡量PK参数具有统计学意义。另一方面，同时使用大小和成熟功能对于一岁以下的婴儿来说具有统计学意义。总之，利用临床数据成功地对儿科患者进行了总体PK建模。大小和成熟函数按既定标准应用，一岁以上儿童可单独使用大小和成熟函数，而大小和成熟函数更适用于新生儿和婴儿的PK分析。
Traditionally, dosage for pediatric patients has been optimized using simple weight-scaled methods, but these methods do not always meet the requirements of children. To overcome this discrepancy, population pharmacokinetic (PK) modeling of size and maturation functions has been proposed. The main objective of the present study was to evaluate a new modeling method for pediatric patients using clinical data from three different clinical studies. To develop the PK models, a nonlinear mixed effect modeling method was employed, and to explore PK differences in pediatric patients, size with allometric and maturation with Michaelis-Menten type functions were evaluated. Goodness of fit plots, visual predictive check and bootstrap were used for model evaluation. Single application of size scaling to PK parameters was statistically significant for the over one year old group. On the other hand, simultaneous use of size and maturation functions was statistically significant for infants younger than one year old. In conclusion, population PK modeling for pediatric patients was successfully performed using clinical data. Size and maturation functions were applied according to established criteria, and single use of size function was applicable for over one year ages, while size and maturation functions were more effective for PK analysis of neonates and infants.