Pharmacokinetics and its role in small molecule drug discovery research

Pharmacokinetics (PK), which describes the disposition of a drug in the body, should be a primary consideration in the selection of a drug candidate, ultimately contributing to its eventual clinical success or failure. Accordingly, a sound understanding of PK concepts and an appreciation of the judicious use of PK and related (e.g., metabolism, transporter) data in drug discovery can be beneficial to those involved in the process. This review defines important PK parameters (e.g., clearance, volume of distribution, half‐life), describes methods of PK data analysis (noncompartmental vs. compartmental) and provides an overview of additional concepts such as allometric scaling, PK/pharmacodynamic modeling, and nonlinear PK. Furthermore, the role and strategic use of PK screens in drug discovery are discussed. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 5, 382–396, 2001