Pharmacokinetics in Drug Discovery

The aim of this current review is to summarize the present status of pharmacokinetics in Drug Discovery. The review is structured into four sections. The first section is a general overview of what we understand by pharmacokinetics and the different LADMET aspects: Liberation, Absorption, Distribution, Metabolism, Excretion, and Toxicity. The second section highlights the different computational or in silico approaches to estimate/predict one or several aspects of the pharmacokinetic profile of a discovery lead compound. The third section discusses the most commonly used in vitro methodologies. The fourth and last section examines the various approaches employed towards the pharmacokinetic assessment of discovery molecules; including all the LADME processes, discussing the different mathematical methodologies available to establish the PK profile of a test compound; what the main differences are and what should be the criteria for using one or another mathematical approach. The major conclusion of this review is that the use of the appropriate preclinical assays has a key role in the long-term viability of a pharmaceutical company since applying the right tools early in discovery will play a key role in determining the company's ability to discover novel safe and effective therapeutics to patients as quickly as possible. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:654–690, 2008