In vitro ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) screening during the lead optimization of drug discovery stage has been proven to have an impact on selecting drug candidates with an enhanced probability of success in clinical trials. Many investigational new drug (IND) applications fail during preclinical and clinical development. It was estimated that poor pharmacokinetic properties and toxicity of the drug account for the majority of the reasons for the high attrition rate. Since the late stage of the drug development cycle usually is a lengthy and costly process, any means of identifying any drug candidates with potential pharmacokinetics and toxicity liabilities in the earlier stage will have a huge impact on the whole drug discovery process. In the past years, this “fail early, fail cheaply” strategy has been adopted by the pharmaceutical industry. It was made possible by the recent advent of in vitro testing systems (e.g. hepatocytes, liver microsomes), improvement on analytical instrument such as high-throughput tandem mass spectrometry LC/MS/MS systems, and introduction of robotic automation systems.

In vitro ADMET screening is now commonly applied in lead optimization of drug discovery process, usually in parallel with approaches for optimizing biochemical and cellular activities of the compounds.