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@ARTICLE{Neumaier:897165,
      author       = {Neumaier, Felix and Zlatopolskiy, Boris D. and Neumaier,
                      Bernd},
      title        = {{D}rug {P}enetration into the {C}entral {N}ervous {S}ystem:
                      {P}harmacokinetic {C}oncepts and {I}n {V}itro {M}odel
                      {S}ystems},
      journal      = {Pharmaceutics},
      volume       = {13},
      number       = {10},
      issn         = {1999-4923},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {FZJ-2021-03655},
      pages        = {1542 -},
      year         = {2021},
      abstract     = {Delivery of most drugs into the central nervous system
                      (CNS) is restricted by the blood–brain barrier (BBB),
                      which remains a significant bottleneck for development of
                      novel CNS-targeted therapeutics or molecular tracers for
                      neuroimaging. Consistent failure to reliably predict drug
                      efficiency based on single measures for the rate or extent
                      of brain penetration has led to the emergence of a more
                      holistic framework that integrates data from various in
                      vivo, in situ and in vitro assays to obtain a comprehensive
                      description of drug delivery to and distribution within the
                      brain. Coupled with ongoing development of suitable in vitro
                      BBB models, this integrated approach promises to reduce the
                      incidence of costly late-stage failures in CNS drug
                      development, and could help to overcome some of the
                      technical, economic and ethical issues associated with in
                      vivo studies in animal models. Here, we provide an overview
                      of BBB structure and function in vivo, and a summary of the
                      pharmacokinetic parameters that can be used to determine and
                      predict the rate and extent of drug penetration into the
                      brain. We also review different in vitro models with regard
                      to their inherent shortcomings and potential usefulness for
                      development of fast-acting drugs or neurotracers labeled
                      with short-lived radionuclides. In this regard, a special
                      focus has been set on those systems that are sufficiently
                      well established to be used in laboratories without
                      significant bioengineering expertise.},
      cin          = {INM-5},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34683835},
      UT           = {WOS:000712777400001},
      doi          = {10.3390/pharmaceutics13101542},
      url          = {https://juser.fz-juelich.de/record/897165},
}