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In Vitro and In Vivo Metabolism Studies

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Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays

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Abstract

Drug metabolism studies play a critical role in the discovery and development of new chemical entities. These studies provide in-depth understanding of absorption, distribution, metabolism, and excretion (ADME) properties of a drug. Optimization of these properties is important to ensure that the exposure is sufficient to achieve proof of concept, and ultimately efficacy and safety in clinical trials to address unmet medical need. In the past two decades, multiple in silico, in vitro, and in vivo ADME tools have been developed and implemented in various stages of the drug discovery and development process to alert chemists of potential ADME issues in the clinic. Most of the ADME studies in drug discovery are conducted using cold material. However, ADME studies in drug development are generally conducted using radiolabeled (3H or 14C) material. The use of radiolabeled material offers a unique mode of quantification of total drug-related molecules.

This chapter describes, in detail, the utility and the challenges of these tools both with in vitro and in vivo metabolism studies that are used to design better molecules that have properties that include lower systemic clearance, and also assist in the selection of nonclinical species for use in safety assessment studies in preclinical development. Additionally, these tools aid in the understanding of reactive metabolites to avoid idiosyncratic adverse drug reactions. Practical case examples are provided.

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Acknowledgments

We thank Allyson Jenkins, Agios, for her editorial assistance.

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Authors and Affiliations

  1. Pyxis Oncology, Boston, MA, USA

    Biplab Das

  2. Department of Drug Metabolism, Pharmacokinetics and Clinical Pharmacology, Agios Pharmaceuticals, Cambridge, MA, USA

    Chandra Prakash

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  1. Biplab Das
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Correspondence to Chandra Prakash .

Editor information

Editors and Affiliations

  1. CorDynamics, Dieburg, Hessen, Germany

    Franz J. Hock

  2. CorDynamics, Chicago, IL, USA

    Michael R. Gralinski

  3. Cytokinetics (United States), South San Francisco, CA, USA

    Michael K. Pugsley

Section Editor information

  1. Toxicology, Cytokinetics, South San Francisco, CA, USA

    Michael K. Pugsley

  2. Safety Pharm Consultant, Dieburg, Germany

    Franz J. Hock DSc

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Das, B., Prakash, C. (2023). In Vitro and In Vivo Metabolism Studies. In: Hock, F.J., Gralinski, M.R., Pugsley, M.K. (eds) Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays. Springer, Cham. https://doi.org/10.1007/978-3-030-73317-9_96-1

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  • DOI: https://doi.org/10.1007/978-3-030-73317-9_96-1

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  • Print ISBN: 978-3-030-73317-9

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