In-Silico ADME Modeling

  • Hans Matter
  • Wolfgang Schmider
Reference work entry


The pressure on research efficiency and cost in the pharmaceutical industry has resulted in a paradigm shift to bring active molecules earlier to the market (Wess 2002; Lawrence 2002). Increasing expenses by attrition in late stage development are partially attributed to an inadequate understanding of pharmacokinetic and toxicological behavior of drugs (Prentis et al. 1988; Kennedy 1997; Drews 2000). The conversion of biologically active molecules into effective and safe pharmaceuticals adds substantial value to the drug discovery process. Consequently, the improvement of a compound profile toward a clinical candidate is one of the essential skills in integrated drug discovery teams. Those candidate requirements include multiple parameters including potency and efficacy, selectivity against related proteins or “antitargets,” favorable physicochemical and pharmacokinetic properties leading to the required bioavailability after oral administration, and an acceptable half-life of elimination of the final candidate. A simultaneous optimization of multiple parameters in carefully planned iterations is therefore required to arrive at molecules with suitable properties and profiles.


Quantitative Structure Activity Relationship Quantitative Structure Activity Relationship Model Polar Surface Area Comparative Molecular Field Analysis ADME Property 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to thank K.H. Baringhaus, A. Dudda, C. Giegerich, G. Hessler, U. Kürzel, K. Mertsch, M. Müller, F. Schmidt, R. Vaz (all Sanofi-Aventis), A. Kohlmann (Ariad), G. Schneider (ETH Zürich), and G. Cruciani (University of Perugia) for many interesting discussions on experimental data and in silico ADME models.

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.R&D, Lead Generation and Candidate RealizationSanofi Deutschland GmbHFrankfurt am MainGermany
  2. 2.R&D, Disposition, Safety and Animal ResearchSanofi Deutschland GmbHFrankfurt am MainGermany

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