Chapter 3 - ADME in Drug Discovery

Abstract

Absorption distribution metabolism excretion (ADME) studies are critical in modern drug discovery. The editorial review and scientific body of writing on this subject is impressive and no exhaustive review will be attempted here. Rather the authors have considered the toxicology student audience and have focused on the more important scientific principles. It is our goal that readers new to this subject will hopefully come away with a basic understanding of where their attention should lie when considering ADME issues in drug discovery and development. The critical concepts can be divided into two areas: Whether the compound (chemical template) exhibits drug-like (a.k.a., drug-able) pharmacokinetic properties and whether the compound has properties that will cause safety concerns in man. Clearance and bioavailability are the most important considerations in the first instance, and toxicity primarily related to ADME, such as DDIs (drug–drug interactions) and metabolism-related idiosyncratic drug reactions, are the most important considerations in the second instance. An early characterization of these properties, eliminating compounds and templates with unacceptable pharmacokinetic (ADME) characteristics, is critical to successful drug discovery programs. This chapter will provide an overview of the most relevant and important areas for the professional toxicologist to understand, and as such presents a snapshot overview of ADME in drug discovery, which is now commonly termed early ADME (eADME).