Why Do We Need In Vivo Models in Drug Metabolism?

Abstract

Despite the significant improvements in the use of in silico and in vitro models in drug metabolism, preclinical animal experiments are still required to fully understand drug disposition. Most drug discovery and development programs target human disease and so such in vivo experiments must be translatable to human. This is a problem since animals express different drug metabolizing enzymes and drug transporters and have different blood flow values to those in human. Consequently, pharmacokinetics and disposition can be very different between animals and humans. In general, passive processes (such as oral absorption, distribution of unbound drug and passive renal elimination scale well from animals to human. Scaling of active processes (such as metabolism and drug transport) can be prone to significant species differences, and require significant care in extrapolation to human. Due to gut physiology and species differences in metabolism, preclinical food effects and drug‐drug interaction studies are not recommended.