Chapter 6: Human in Vitro ADMET and Prediction of Human Pharmacokinetics and Toxicity Liabilities at the Discovery Stage Check Access

The drug development process has undergone a rapid evolution due to an expanding biological and chemical toolbox that allows novel target identification and rapid synthesis of a large number of diverse chemical libraries. The discovery of novel therapeutics is an inherently complex and interdisciplinary process, which requires close integration of scientists from several disciplines in an environment in which lessons are shared and taught across an organisation. However, traditionally the industry suffered from the lack of integration between chemists and biologists. Each discipline produced results that were scientifically valid, but frequently had little relevance to the likelihood of launching a commercial product. ADMET is an area that has emerged over the past 15 years and has created a unique interdisciplinary interface between medicinal chemists, biologists, formulators, toxicologists, clinicians and regulators. The implementation of ADMET profiling of drug candidates in conjunction with biological efficacy optimisation has dramatically reduced drug failures in clinical trials for pharmacokinetic reasons and has become a lingua franca between disciplines that are involved in drug development. The goal of an ADMET programme is to guide candidate selection by identifying molecules with optimal potency and drug-like properties. The purpose of this chapter is to briefly review the current state-of-the-art of ADMET and its scientific principles and describe some of the most prevalent ADMET strategies used to de-risk drug discovery programmes.