Posological review of dose extrapolation methodologies in animal studies, early-phase clinical trials and special populations

Abstract

Identifying the right dose is arguably an essential step in the design of experiments related to drug discovery and development. Often, dose extrapolation is done to scale the doses of a drug from one species to another. However, literature is replete with cases that warrant against the careless and inadequate application of dose-extrapolation methodologies. Increasing costs of research and the development and ethical considerations of experimentation in animals and humans do not condone injudicious design of experiments. This call to caution forms the essential premise of the current review, which focuses on the methodology of the dose extrapolation and its place in early-phase clinical trials and animal studies. Furthermore, the review also provides an update on within-species dose extrapolation to address the issues of adapting adult human doses to pediatric and geriatric settings.