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Distribution: Across Barriers

  • Tanja Eisenblaetter
  • Yohannes Hagos
  • Saskia Flörl
  • Annett Kühne
Reference work entry

Abstract

Distribution of drugs across barriers plays a predominant role in the processes of absorption (A), distribution (D), and excretion (E) and is thus a major determinant of a drugs pharmacokinetic profile. The barrier at the site of absorption is in most cases built by the enterocytes of the small intestine (see Chap.  29 “Absorption: In Vivo Tests (Radiolabeled)”). Apart from lung, heart, muscle, and brain, the main target organs are kidney and liver which are also the major elimination pathways of drugs. Cell membranes of liver hepatocytes and kidney cells have to be passed in these cases. The brain plays a special role in the distribution of drugs because drugs normally should not enter the central nervous system to avoid severe adverse effects. It is, therefore, protected by the very tight blood–brain barrier. However, when the target is located in the brain, the drug needs to cross this barrier. Meanwhile, there exist several in vitro systems to study drug permeation across this special blood–brain barrier (Sect. 36.1). They cover primary cultures of brain endothelial cells in monoculture or as coculture with astrocytes or pericytes (Sect. 36.1.1), immortalized endothelial cell lines from different species (Sect. 36.1.2), and surrogate models (Sect. 36.1.3).

Keywords

Madine Darby Canine Kidney Multidrug Resistance Protein Madine Darby Canine Kidney Cell Brain Capillary Endothelial Cell RBE4 Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Tanja Eisenblaetter
    • 1
  • Yohannes Hagos
    • 2
  • Saskia Flörl
    • 3
  • Annett Kühne
    • 3
  1. 1.R&D Drug Metabolims and PharmacokineticsSanofi Deutschland GmbHFrankfurt am MainGermany
  2. 2.Department of Vegetative Physiology and PathologyGeorg-August UniversityGöttingenGermany
  3. 3.PortaCellTec biosciences GmbHGöttingenGermany

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