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Understanding transport through pharmacological barriers — are we there yet?

Nature Reviews Drug Discovery volume 9, pages 897–898 (2010)Cite this article

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Recently, three papers have been published in Nature Reviews Drug Discovery that deal with the concepts, problems and regulatory aspects of drug transport across biological membranes (Nature Rev. Drug Discov. 9, 597–614 (2010); Nature Rev. Drug Discov. 9, 215–236 (2010); Nature Rev. Drug Discov. 7, 205–220 (2008))1,2,3. The articles emphasize different aspects of drug permeation across pharmacological barriers, concentrating either on the role of carrier proteins (such as ATP-binding cassette (ABC) transporters and solute carrier proteins)3 or on the relevance of passive diffusion and its coexistence with carrier-mediated pathways1. More importantly, these papers direct the limelight to a field that has been long characterized by confusion and neglect.

The classical approach of membrane biophysics and membrane biochemistry regarded the cell membrane as an efficient barrier for hydrophilic compounds (especially those that are ionized), whereas a rapid passive permeation was granted for hydrophobic compounds. Accordingly, basic textbook terms such as 'semi-permeability', 'diffusion' and 'reflection coefficient', as well as the properties of carriers and transporters, were defined as if they existed in water-based solutions. However, following the discovery of ABC multidrug transporters, it was recognized that laws governing drug permeation across the lipid phase of the membrane are more complex and that these laws could not be analysed using the classical approach.

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Authors and Affiliations

  1. Balázs Sarkadi is at the Membrane Research Group of the Hungarian Academy of Sciences, Dioszegi 64, 1113 Budapest, Hungary.,

    Balázs Sarkadi

  2. Gergely Szakács is at the Institute of Enzymology, Hungarian Academy of Sciences, Karolina 29, 1113 Budapest, Hungary.,

    Gergely Szakács

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  1. Balázs Sarkadi
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  2. Gergely Szakács
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Correspondence to Balázs Sarkadi or Gergely Szakács.

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Sarkadi, B., Szakács, G. Understanding transport through pharmacological barriers — are we there yet?. Nat Rev Drug Discov 9, 897–898 (2010). https://doi.org/10.1038/nrd3187-c1

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