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Brain Distribution of Drugs: Brain Morphology, Delivery Routes, and Species Differences

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Physiology, Pharmacology and Pathology of the Blood-Brain Barrier

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 273))

Abstract

Neuropharmacokinetics considers cerebral drug distribution as a critical process for central nervous system drug action as well as for drug penetration through the CNS barriers. Brain distribution of small molecules obeys classical rules of drug partition, permeability, binding to fluid proteins or tissue components, and tissue perfusion. The biodistribution of all drugs, including both small molecules and biologics, may also be influenced by specific brain properties related to brain anatomy and physiological barriers, fluid dynamics, and cellular and biochemical composition, each of which can exhibit significant interspecies differences. All of these properties contribute to select optimal dosing paradigms and routes of drug delivery to reach brain targets for classical small molecule drugs as well as for biologics. The importance of these properties for brain delivery and exposure also highlights the need for efficient new analytical technologies to more comprehensively investigate drug distribution in the CNS, a complex multi-compartmentalized organ system.

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Paris, Paris, France

    Fanchon Bourasset, Sylvain Auvity & Jean-Michel Scherrmann

  2. INSERM UMR-S1144, Paris, France

    Fanchon Bourasset, Sylvain Auvity & Jean-Michel Scherrmann

  3. Denali Therapeutics, Inc., South San Francisco, CA, USA

    Robert G. Thorne

  4. Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, USA

    Robert G. Thorne

Authors
  1. Fanchon Bourasset
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  2. Sylvain Auvity
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  3. Robert G. Thorne
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  4. Jean-Michel Scherrmann
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Correspondence to Robert G. Thorne or Jean-Michel Scherrmann .

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Editors and Affiliations

  1. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

    Zameel Cader

  2. Center for Health and Bioresources, AIT Austrian Institute of Technology GmbH, Wien, Austria

    Winfried Neuhaus

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Bourasset, F., Auvity, S., Thorne, R.G., Scherrmann, JM. (2020). Brain Distribution of Drugs: Brain Morphology, Delivery Routes, and Species Differences. In: Cader, Z., Neuhaus, W. (eds) Physiology, Pharmacology and Pathology of the Blood-Brain Barrier. Handbook of Experimental Pharmacology, vol 273. Springer, Cham. https://doi.org/10.1007/164_2020_402

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