ABSTRACT
The extrapolation of experimental data to predict efficacy and toxicity from preclinical species to humans is one of the major steps in drug development. Given the differences in physiological, pharmacological, and pharmacokinetic processes between laboratory animals and humans, the extrapolation based on doses given in mg/kg or mg/m is mostly inaccurate. The pharmaceutical industry has focused on the evaluation and prediction of clinically relevant metabolic-based drug–drug interactions. For a large number of drugs, dose selection is difficult for the main toxicity studies, therefore, the dose range-finding studies are of great value. The qualitative similarity in metabolic profiles in nonclinical safety species and humans provides assurance regarding the validity of selected species for human risk assessment. Prior to exposing humans to a new drug entity, especially belonging to a new pharmacological mechanism and/or structure, it is critical to know what adverse effects may occur and whether they are reversible.
