How to read the science
Methodological notes for interpreting evidence with sound judgment.
Dose extrapolation in humans
*⏱ 1 min read
Animal models widely used in biomedical research to predict the toxicity, safety, and efficacy of interventions in humans are complicated by differences in the metabolism of xenobiotics or drugs between animals and humans, differences that arise from physiological, anatomical, metabolic, life-span, and genetic diversity among species, which makes a conversion method necessary to translate the results of animal studies into dose recommendations for people.
A simple empirical approach called allometric scaling makes it possible to scale and normalize a dose according to differences in body surface area in order to extrapolate doses from animal science to human research, resulting in a species-specific correction factor; for example, a dose of 10 mg/kg of body weight in rats is divided by a correction factor of 6.2, resulting in an approximation of 1.62 mg/kg in humans for the same compound, whereas in mice the same calculation involves dividing by 12.3, resulting in 0.821 mg/kg in humans.
The key principles of allometric scaling that are important to understand are: larger animals have lower metabolic rates; the physiological processes of larger animals are slower; larger animals require relatively smaller drug doses based on body weight; allometric scaling should not be applied to extrapolate doses from adults to children; and the US FDA has established guidelines for determining the human equivalent dose in clinical trials based on this body surface area principle.