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Protocols in In Vitro Hepatocyte Research pp 287–302Cite as

Analysis of Sinusoidal Drug Uptake Transporter Activities in Primary Human Hepatocytes

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1250))

Abstract

Hepatic drug transporters play an important role in pharmacokinetics and drug–drug interactions. Among these membrane transporters, the sodium taurocholate cotransporting polypeptide (NTCP/SLC10A1), the organic anion transporting polypeptides (OATPs) 1B1 (SLCO1B1), 1B3 (SLCO1B3) and 2B1 (SLCO2B1), the organic anion transporter 2 (OAT2/SLC22A7) and the organic cation transporter 1 (OCT1/SLC22A1) are likely major ones, notably mediating sinusoidal uptake of various drugs or endogenous compounds, like bile acids, from blood into hepatocytes. Studying putative interactions of drugs, including those in development processes, with these transporters is an important issue. For this purpose, cultured human hepatocytes, that exhibit functional expression of NTCP, OATPs, OAT2 and OCT1, are considered as a relevant in vitro cellular model. This chapter describes a method allowing to accurately analyze NTCP, OATP, OAT2 and OCT1 transport activities in primary human hepatocyte cultures, which can be applied to the determination of potential interactions of drugs with these hepatic uptake transporters.

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Acknowledgements

We would like to thank the Biological Resource Center (CHU Rennes) for providing us with human hepatocyte suspensions.

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Authors and Affiliations

  1. Faculté de Pharmacie, Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Université de Rennes 1, 2 Avenue Pr Leon Bernard, Rennes, 35043, France

    Marc Le Vée, Elodie Jouan & Olivier Fardel

  2. Centre de Pharmacocinétique, Technologie Servier, Orléans, France

    Claire Denizot & Yannick Parmentier

  3. Pôle Biologie, Centre Hospitalier Universitaire, Rennes, France

    Olivier Fardel

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  1. Marc Le Vée
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  2. Elodie Jouan
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  3. Claire Denizot
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  4. Yannick Parmentier
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  5. Olivier Fardel
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Corresponding author

Correspondence to Olivier Fardel .

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Editors and Affiliations

  1. Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels, Belgium

    Mathieu Vinken

  2. Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels, Belgium

    Vera Rogiers

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Le Vée, M., Jouan, E., Denizot, C., Parmentier, Y., Fardel, O. (2015). Analysis of Sinusoidal Drug Uptake Transporter Activities in Primary Human Hepatocytes. In: Vinken, M., Rogiers, V. (eds) Protocols in In Vitro Hepatocyte Research. Methods in Molecular Biology, vol 1250. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2074-7_21

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  • DOI: https://doi.org/10.1007/978-1-4939-2074-7_21

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2073-0

  • Online ISBN: 978-1-4939-2074-7

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