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儿科生理学的年龄相关性变化:器官重量和血流的定量分析:儿科生理学的年龄相关性变化。

Age-Related Changes in Pediatric Physiology: Quantitative Analysis of Organ Weights and Blood Flows : Age-Related Changes in Pediatric Physiology.

机构信息

Department of Pharmaceutical Sciences, 455 Pharmacy Building, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, 14214-8033, USA.

Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA.

出版信息

AAPS J. 2021 Mar 31;23(3):50. doi: 10.1208/s12248-021-00581-1.

Abstract

Development of comprehensive and updated quantitative relationships between physiological parameters and age for pediatrics remains to be accomplished. Towards this goal, we have performed a thorough literature search and collected published data on organ weights and organ blood flow rates for 0-20-year-old male and female human subjects. The data were used to develop continuous relationships between physiological parameters and age, using a single form of mathematical equation. Four sets of equations (0-2 years male, 0-2 years female, 2-20 years male, 2-20 years female) for the body weight vs. age, height vs. age, and organ weight vs. age relationships and 2 sets of equations (0-20 years male, 0-20 years female) for organ flow rate vs. age relationship were developed. The variability of each physiological parameter was also estimated, and the equations allow simulation of a virtual population for a specific age, weight, and sex. We further compared the physiological parameters vs. age curves simulated using our equations to the existing databases (Simcyp Simulator and PK-Sim). The predicted physiological parameters were comparable between our study and the existing databases, validating our equation's utility. Additionally, we described body weight-normalized organ weights and organ blood flow rates as a function of age, to provide an insight into how the contribution of each organ towards total body weight and total blood flow changes throughout ontogenesis. The physiological parameter database and equations presented here can serve as an open source to facilitate the development of pediatric physiologically based pharmacokinetic models.

摘要

目前仍需开发全面且最新的儿科生理参数与年龄间的定量关系。为此,我们进行了全面的文献检索,并收集了已发表的 0 至 20 岁男性和女性人体器官重量和器官血流率数据。我们使用单一数学方程形式,根据这些数据建立了生理参数与年龄之间的连续关系。我们开发了四组方程(0-2 岁男性、0-2 岁女性、2-20 岁男性、2-20 岁女性),用于描述体重与年龄、身高与年龄、器官重量与年龄的关系,以及两组器官血流率与年龄的关系。我们还估计了每个生理参数的变异性,这些方程允许针对特定年龄、体重和性别模拟虚拟人群。我们进一步将使用我们的方程模拟的生理参数与年龄曲线与现有的数据库(Simcyp Simulator 和 PK-Sim)进行了比较。我们的研究与现有数据库中预测的生理参数具有可比性,验证了我们方程的实用性。此外,我们还描述了体重归一化的器官重量和器官血流率随年龄的变化,深入了解每个器官在整个个体发生过程中对体重和总血流的贡献如何变化。这里提供的生理参数数据库和方程可以作为一个开源资源,有助于开发儿科生理药代动力学模型。

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