Misconceptions and issues regarding allometric scaling during the drug development process.

INTRODUCTION: Allometry is the study of size and its consequences. The simple hypothesis of allometric scaling is that all physiological parameters are proportional to body size or body mass. This review examines the development of theory-based allometry or fixed exponents (0.75 and 1.0 for basal metabolic rate and volume, respectively) and the evidence for or against the theory. The main focus of this report is to show the readers that there is enough evidence from experimental data that negate the concept of theory-based allometry in biology, physiology, and pharmacokinetics. Areas covered: In this review, the history of the development of theoretical allometry and the strong evidence against theory-based allometry demonstrated by experimental data is provided. During drug development, allometry is applied to both inter-species (from animals to humans) and intra-species (adults to children) scaling. These two forms of allometric scaling in the context of theory-based allometry are discussed and provide insight on scientific progress that refute theory-based allometry. Expert opinion: Theory-based allometry is a mere theory and experimental data and real-life observations strongly negate the existence of such a theory. Pharmacostatistical and physiological models based on theory-based allometry can be misleading and incorrect because the theory-based allometric exponent 0.75 is not universal. The exponents of allometry are data dependent and are not fixed in the universe.