In Vitro and In Silico ADME Prediction

Pharmacokinetic issues have been identified as a major cause for the attrition of new chemical entities in drug discovery. High development costs and time investments are associated with the discovery of such issues during clinical drug development. To overcome this problem, various in vitro and in silico ADME (Absorption, Distribution, Metabolism, Excretion) tools have been developed to predict drug pharmacokinetics using only a minimal amount of experimental data. Selecting the most appropriate option(s) from this broad range of in vitro and in silico ADME tools is challenging for drug discovery scientists as it requires consideration of a number of factors including the stage of the discovery process, any data already generated for a lead molecule or series and an awareness of the limitations and advantages of each ADME tool. ADME parameters, obtained through experimental approaches and/or in silico prediction, are also essential inputs to physiologically-based pharmacokinetic models for the prediction of in vivo pharmacokinetics. Available in vitro and in silico ADME tools are presented and assessed in the following book chapter.