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

Age-Related Changes in Pediatric Physiology

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.

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Chang, H.P., Kim, S.J., Wu, D. et al. Age-Related Changes in Pediatric Physiology: Quantitative Analysis of Organ Weights and Blood Flows. AAPS J 23, 50 (2021). https://doi.org/10.1208/s12248-021-00581-1

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KEY WORDS

  • organ blood flow
  • organ weight
  • PBPK
  • pediatrics
  • pharmacokinetics
  • physiological parameters