In Silico ADME Approaches

During the past decade, the pharmaceutical industry has invested considerably in technologies that have the potential to increase throughput in discovery projects. With the increase in the numbers of molecules synthesized in a typical drug discovery program, as well as the large amount of information utilized in the selection of a drug candidate, it is very useful and necessary ADME and pharmacokinetic information during the discovery process. Over the past decade, many in vitro, and even in vivo, ADME/PK screening have been developed and routinely deployed to generate this information in support of drug discovery efforts. In the past few years, alternative methods as in silico methods have been published. The great challenge for in silico methods is generation of models that correlate more closely with in vivo systems. This review attempts to summarize the in silico approaches taking into account the (i) ways of evaluating a molecule for ADME properties (type of descriptor) and (ii) the employed method for prediction of ADME properties. Progress in this area will be discussed, focussing on oral absorption, blood-brain barrier and metabolism, and some aspects on excretion will be also briefly commented.

Keywords: Oral absorption, blood-brain barrier, metabolism, excretion, ADME, in silico, QSPR, CYPs