Metabolism Pharmacology

Safety pharmacology defines studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above and applies to new chemical entities, biotechnology-derived products, and marketed pharmaceuticals when appropriate. Evaluation of undesirable pharmacodynamic effects of new chemical entities on metabolism is of secondary importance in safety pharmacology. This is because most metabolic organs are not part of the “Core Battery System,” consisting of the central nervous system, cardiovascular system, and respiratory system. Here, we describe pharmacological methods for the characterization of candidate compounds on their effects on the gastrointestinal functions (gastric acid secretion, bile secretion, exocrine pancreatic secretion, gastrointestinal motility) and their gastrointestinal injury potential. We present pharmacological methods aiming to elucidate the potential undesirable effect of compounds on intermediary carbohydrate and lipid metabolism resulting in hypo- or hyperglycemia, hyperlipidemia, and insulin resistance, which can ultimately provoke life-threatening hypoglycemia or evolve to diabetes, atherosclerosis, and obesity. We also present assays that meet the ICH guideline and that are appropriately adapted for the assessment of potential pharmacological side effects on metabolism pharmacology.