The impact of early ADME profiling on drug discovery and development strategy
Jianling Wang, László Urbán · 2004
The increased costs in the discovery and development of new drugs, due in part to the high attrition rate of drug candidates in development, has led to a new strategy to introduce early, parallel evaluation of efficacy and biopharmaceutical properties of drug candidates. Investigation of terminated projects revealed that the primary cause for drug failure in the development phase was the poor pharmacokinetic and ADMET (Absorption, Distribution, Metabolism, Discretion and Toxicity) properties rather than unsatisfactory efficacy. In addition, the applications of parallel synthesis and combinatory chemistry to expedite lead finding and lead optimisation processes has shifted the chemical libraries towards poorer biopharmaceutical properties. Establishments of high throughput and fast ADMET profiling assays allow for the prioritisation of leads or drug candidates by their biopharmaceutical properties in parallel with optimisation of their efficacy at early discovery phases.This is expected to not only improve the overall quality of drug candidates and therefore the probability of their success, but also shorten the drug discovery and development process. In this article, we review the early ADME profiling approach, their timing in relation to the entire drug discovery and development process and the latest technologies of the selected assays will be reviewed.