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Pharmaceutical drug transport: the issues and the implications that it is essentially carrier-mediated only.

Drug Discovery Today

metabolism, Pharmaceutical Preparations, Membranes, Artificial, Membrane Transport Proteins, Humans, Gene Expression Profiling, Drug Design, Cell Membrane Permeability, Cell Membrane, Biological Transport, Animals

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      Abstract

      All cells necessarily contain tens, if not hundreds, of carriers for nutrients and intermediary metabolites, and the human genome codes for more than 1000 carriers of various kinds. Here, we illustrate using a typical literature example the widespread but erroneous nature of the assumption that the 'background' or 'passive' permeability to drugs occurs in the absence of carriers. Comparison of the rate of drug transport in natural versus artificial membranes shows discrepancies in absolute magnitudes of 100-fold or more, with the carrier-containing cells showing the greater permeability. Expression profiling data show exactly which carriers are expressed in which tissues. The recognition that drugs necessarily require carriers for uptake into cells provides many opportunities for improving the effectiveness of the drug discovery process. Copyright © 2011 Elsevier Ltd. All rights reserved.

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      21624498
      10.1016/j.drudis.2011.05.010

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