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

Abstract

AbstractA generic quantitative equation for describing the ontogeny of human metabolic processes from infancy to adulthood has broad implications in biology, clinical medicine and drug discovery. In this paper, we infer quantitative knowledge of human ontogeny from a systematic analysis of diverse datasets related to basal metabolic rate (BMR), glomerular filtration rate (GFR) and drug clearance (CL). The datasets contain bodyweight-specific values of the three physiological quantities spanning neonates and adults. Ontogenetic data were either directly taken from the literature or generated from existing models, which universally show biphasic curves of bodyweight scaling on log-log coordinates. Accordingly, a biphasic-allometry equation was proposed and evaluated as a general model using nonlinear regression. The proposed equation consists of two allometric terms in the form of reciprocals that asymptotically determine the overall curvature. Specifically, the biphasic curve is characterized by superlinear (slope >1) and sublinear (slope <1) phases of bodyweight scaling. Phase transition occurs at a critical bodyweight, which could be estimated from fitted model parameters. Overall, the proposed model is versatile in the sense that it fits satisfactorily to all datasets. Moreover, through further derivation and generalization, the model reveals the similarities and differences among ontogenetic processes. In conclusion, the ontogenetic development of important human functions can be modeled by a novel mixed-allometry equation.