ABSTRACT
A recent survey showed that the attrition rate related to absorption, metabolism, distribution, and excretion (ADME) and pharmacokinetic (PK) failures has dropped from 40% to 50% in 1991 [1-3] to approximately 10% in 2000 [2,4]. Such a dramatic improvement within approximately one decade did not happen by chance. It was driven by the recognition of the impact of ADME and PK attributes on the safety, ef cacy, and developability of new drug candidates and allocating necessary resources to address them early in drug discovery. However, recent advances in synthetic processes, which have generated enormous numbers of new chemical entities (NCEs) over the past few years, have created the need to design new high-throughput solutions to allow rapid assessment of the drug metabolism and pharmacokinetic (DMPK) attributes of potential drug candidates without compromising the quality of the data [5]. As a result, innovative in vitro ADME and PK approaches [6-15] are now routinely used in the pharmaceutical industry to evaluate DMPK attributes. Therefore, compounds with undesirable DMPK characteristics can be screened out as early, as quickly and as cheaply as possible, so that available resources can be focused on the promising drug candidates that survive this screening process.
