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Transport of Drugs

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Physiology and Pharmacology of the Blood-Brain Barrier

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 103))

Abstract

The blood-brain barrier (BBB) at cerebral capillaries consists of a continuous layer of endothelial cells connected by tight junctions (zonulae occludens). The capillary wall lacks water-filled channels of suitable size for aqueous diffusion (except for water itself), and the endothelial cell membranes lack carrier systems of suitable affinity for mediated transport of most drugs [with notable exceptions, such as l-dihydroxyphenylalanine (l-DOPA), melphalan; see below]. Also, it is unlikely that vesicular transport plays a significant role in solute transfer across the BBB (Rapoport and Robinson 1986). Therefore, most drugs pass between blood and brain extracellular fluid via the lipid membranes of the endothelial cells. To do so, they first must leave the aqueous medium of the blood, then pass into the membrane lipid, diffuse across the membrane, enter and diffuse across the endothelial cell cytoplasm, enter and diffuse across the abluminal membrane, and finally enter the aqueous medium on the other side. Alternatively, the drug could diffuse around the circumference of the endothelial cell via tight junctions and interendothelial cell gaps, thereby bypassing the intracellular and transmembrane diffusion steps.

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Abbreviations

BUI:

Brain uptake index

AIB:

?-Aminoisobutyric acid

E:

Extraction fraction

BBB:

Blood-brain barrier

L-DOPA:

L-dihydroxphenylalanine

BSP:

Sulfobromophthalein

PA:

Permeability-surface area product

BTB:

Blood-tumor barrier

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Authors
  1. P. J. Robinson
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  2. S. I. Rapoport
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Editor information

Editors and Affiliations

  1. Physiology Group Biomedical Sciences Division King’s College London, University of London, Strand, WC2R 2LS, London, Great Britain

    Michael W. B. Bradbury M.A., D.M. (Oxon)

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© 1992 Springer-Verlag Berlin Heidelberg

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Robinson, P.J., Rapoport, S.I. (1992). Transport of Drugs. In: Bradbury, M.W.B. (eds) Physiology and Pharmacology of the Blood-Brain Barrier. Handbook of Experimental Pharmacology, vol 103. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76894-1_11

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  • DOI: https://doi.org/10.1007/978-3-642-76894-1_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-76896-5

  • Online ISBN: 978-3-642-76894-1

  • eBook Packages: Springer Book Archive

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