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Metabolism Studies In Vitro and In Vivo

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Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays

Abstract

In the era of combinatorial chemistry and high-throughput screening, a huge number of hits and structural analogs potentially interesting as new chemical entities (NCEs) can be produced in a short period of time. Drug metabolism is a decisive determinant of the pharmacokinetic behavior of these compounds. Approximately three quarters of the top 200 prescribed drugs in the United States in 2002 are cleared by metabolism, one-third are cleared via the kidney, while biliary clearance of unchanged drug plays only a minor role (Williams et al. 2004). Thus, understanding and description of the metabolism of a new chemical entity is an essential part of the submission dossier (Weaver and Jochemsen 2009) as well as an important optimization parameter in drug discovery programs to reduce attrition in drug development (Kola and Landis 2004)

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Notes

  1. 1.

    Selection of an adequate batch of collagenase is the key critical step for successful isolation of human hepatocytes. Whereas the majority of all collagenases allow successful isolation of rat hepatocytes, selection of a good batch for human liver is more critical. Mostly, the collagenase concentration has to be optimized for an individual batch of collagenase.

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  1. Sanofi Deutschland GmbH, Frankfurt am Main, Germany

    Dr. Angela Dudda & Dr. Gert Ulrich Kuerzel

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  1. Dr. Angela Dudda
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  2. Dr. Gert Ulrich Kuerzel
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Correspondence to Angela Dudda .

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  1. Sanofi Pharma Deutschland GmbH, A company of the Sanofi-Aventis Group Industriepark Hoechst, Frankfurt am Main, Germany

    Jochen Maas

  2. Dieburg, Germany

    Franz J. Hock

  3. Idstein, Germany

    Dieter Mayer

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Dudda, A., Kuerzel, G.U. (2013). Metabolism Studies In Vitro and In Vivo. In: Vogel, H.G., Maas, J., Hock, F.J., Mayer, D. (eds) Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25240-2_46

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