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Case Study 7: Transporters Case Studies—In Vitro Solutions for Translatable Outcomes

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Enzyme Kinetics in Drug Metabolism

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2342))

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Abstract

Assessing the interactions of a new drug candidate with transporters, either as a substrate, inhibitor, or inducer, is no simple matter. There are many clinically relevant transporters, as many as nine to be evaluated for an FDA submission and up to 11 for the EMA as of 2020. Additionally, it is likely that if a compound is a substrate or inhibitor of one transporter, it will be so for other transporters as well. There are practically no specific substrates or inhibitors, presumably because the specificities of drug transporters are so broad and overlapping, and even fewer clinically relevant probes that can be used to evaluate transporter function in humans. In the case of some transporters, it is advisable to evaluate an NCE with more than one test system and/or more than one probe substrate in order to convince oneself (and regulatory authorities) that a clinical drug interaction study is not warranted. Finally, each test system has its own unique set of advantages and disadvantages. One has to appreciate the nuances of the available tools (test systems, probe substrates, etc.) to select the most relevant tools for the study and design the optimal in vitro experiment. In this chapter, several examples are used to illustrate the successful interpretation of in vitro data for both efflux and uptake transporters. Some data presented in this chapter are unpublished at the time of the compilation of this book. It has been included in this chapter to provide a sense of the complexities in transporter kinetics to the reader.

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Author information

Authors and Affiliations

  1. Absorption Systems, Exton, PA, USA

    Sid Bhoopathy, Chris Bode, Vatsala Naageshwaran, Venkata Mukkavilli & Ismael J. Hidalgo

  2. MilliporeSigma, EMD Millipore Corporation, Burlington, MA, USA

    Erica Weiskircher-Hildebrandt

Authors
  1. Sid Bhoopathy
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  2. Chris Bode
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  3. Vatsala Naageshwaran
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  4. Erica Weiskircher-Hildebrandt
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  5. Venkata Mukkavilli
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  6. Ismael J. Hidalgo
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Corresponding author

Correspondence to Sid Bhoopathy .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA

    Swati Nagar

  2. Translational Medicine, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA

    Upendra A. Argikar

  3. Independent, Harleysville, PA, USA

    Donald Tweedie

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Bhoopathy, S., Bode, C., Naageshwaran, V., Weiskircher-Hildebrandt, E., Mukkavilli, V., Hidalgo, I.J. (2021). Case Study 7: Transporters Case Studies—In Vitro Solutions for Translatable Outcomes. In: Nagar, S., Argikar, U.A., Tweedie, D. (eds) Enzyme Kinetics in Drug Metabolism. Methods in Molecular Biology, vol 2342. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1554-6_26

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  • DOI: https://doi.org/10.1007/978-1-0716-1554-6_26

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1553-9

  • Online ISBN: 978-1-0716-1554-6

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