4.6 Article

A General Biphasic Bodyweight Model for Scaling Basal Metabolic Rate, Glomerular Filtration Rate, and Drug Clearance from Birth to Adulthood

Journal

AAPS JOURNAL
Volume 24, Issue 3, Pages -

Publisher

SPRINGER
DOI: 10.1208/s12248-022-00716-y

Keywords

allometry; drug clearance; basal metabolic rate; glomerular filtration rate; maturation and growth

Funding

  1. Ministry of Science and Technology (MOST)
  2. Higher Education Sprout Project -Ministry of Education (MOE), Taiwan

Ask authors/readers for more resources

The objective of this study is to propose a unified equation to quantify the changes of human basal metabolic rate, glomerular filtration rate, and drug clearance from infancy to adulthood. The proposed equation shows that these changes can be well described by a biphasic model with two distinct linear segments.
The objective of this study is to propose a unified, continuous, and bodyweight-only equation to quantify the changes of human basal metabolic rate (BMR), glomerular filtration rate (GFR), and drug clearance (CL) from infancy to adulthood. The BMR datasets were retrieved from a comprehensive historical database of male and female subjects (0.02 to 64 years). The CL datasets for 17 drugs and the GFR dataset were generated from published maturation and growth models with reported parameter values. A statistical approach was used to simulate the model-generated CL and GFR data for a hypothetical population with 26 age groups (from 0 to 20 years). A biphasic equation with two power-law functions of bodyweight was proposed and evaluated as a general model using nonlinear regression and dimensionless analysis. All datasets universally reveal biphasic curves with two distinct linear segments on log-log plots. The biphasic equation consists of two reciprocal allometric terms that asymptotically determine the overall curvature. The fitting results show a superlinear scaling phase (asymptotic exponent >1; ca. 1.5-3.5) and a sublinear scaling phase (asymptotic exponent <1; ca. 0.5-0.7), which are separated at the phase transition bodyweight ranging from 5 to 20 kg with a mean value of 10 kg (corresponding to 1 year of age). The dimensionless analysis generalizes and offers quantitative realization of the maturation and growth process. In conclusion, the proposed mixed-allometry equation is a generic model that quantitatively describes the phase transition in the human maturation process of diverse human functions.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available