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Drug Discovery and Evaluation: Methods in Clinical Pharmacology pp 1–15Cite as

Relevance of Transporters in Clinical Studies

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Abstract

It has become clear that drug disposition is not just a result of passive diffusion and metabolizing enzymes. Numerous transporters were identified in recent years to be involved in the absorption, distribution, and excretion of essentially all drugs. While transporters of the solute carrier (SLC) family are mainly involved in the uptake of drugs into cells, ATP-binding cassette (ABC) transporters are responsible for their efflux. Among the more than 420 SLC and 47 ABC transporters, only about 25 seem to be important for the disposition of over-the-counter and prescription drugs. Among these the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) have identified seven transporters which need to be tested for investigational drugs and an additional five transporters that are considered to be important. Two of the seven transporters, the multidrug resistance protein 1 (MDR1) and the breast cancer resistance protein (BCRP), are ABC transporters. The other five, the organic cation transporter 2 (OCT2), the organic anion transporter 1 (OAT1) and 3 (OAT3), and the organic anion transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3), are SLC transporters. If additional transporters become clinically relevant, they may be added by the regulatory agencies to the list or required transporters.

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Acknowledgments

The author would like to acknowledge the National Institutes of Health grant GM077336.

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Authors and Affiliations

  1. Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, KS, USA

    Bruno Hagenbuch

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  1. Bruno Hagenbuch
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Correspondence to Bruno Hagenbuch .

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Editors and Affiliations

  1. CorDynamics , Dieburg, Germany

    Franz J. Hock

  2. CorDynamics , Chicago, Illinois, USA

    Michael R. Gralinski

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Hagenbuch, B. (2018). Relevance of Transporters in Clinical Studies. In: Hock, F., Gralinski, M. (eds) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer, Cham. https://doi.org/10.1007/978-3-319-56637-5_23-1

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  • DOI: https://doi.org/10.1007/978-3-319-56637-5_23-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-56637-5

  • Online ISBN: 978-3-319-56637-5

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