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000897165 1001_ $$0P:(DE-Juel1)175142$$aNeumaier, Felix$$b0$$eCorresponding author
000897165 245__ $$aDrug Penetration into the Central Nervous System: Pharmacokinetic Concepts and In Vitro Model Systems
000897165 260__ $$aBasel$$bMDPI$$c2021
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000897165 520__ $$aDelivery of most drugs into the central nervous system (CNS) is restricted by the blood–brain barrier (BBB), which remains a significant bottleneck for development of novel CNS-targeted therapeutics or molecular tracers for neuroimaging. Consistent failure to reliably predict drug efficiency based on single measures for the rate or extent of brain penetration has led to the emergence of a more holistic framework that integrates data from various in vivo, in situ and in vitro assays to obtain a comprehensive description of drug delivery to and distribution within the brain. Coupled with ongoing development of suitable in vitro BBB models, this integrated approach promises to reduce the incidence of costly late-stage failures in CNS drug development, and could help to overcome some of the technical, economic and ethical issues associated with in vivo studies in animal models. Here, we provide an overview of BBB structure and function in vivo, and a summary of the pharmacokinetic parameters that can be used to determine and predict the rate and extent of drug penetration into the brain. We also review different in vitro models with regard to their inherent shortcomings and potential usefulness for development of fast-acting drugs or neurotracers labeled with short-lived radionuclides. In this regard, a special focus has been set on those systems that are sufficiently well established to be used in laboratories without significant bioengineering expertise.
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000897165 7001_ $$0P:(DE-Juel1)176188$$aZlatopolskiy, Boris D.$$b1
000897165 7001_ $$0P:(DE-Juel1)166419$$aNeumaier, Bernd$$b2
000897165 773__ $$0PERI:(DE-600)2527217-2$$a10.3390/pharmaceutics13101542$$gVol. 13, no. 10, p. 1542 -$$n10$$p1542 -$$tPharmaceutics$$v13$$x1999-4923$$y2021
000897165 8564_ $$uhttps://juser.fz-juelich.de/record/897165/files/Invoice_MDPI_pharmaceutics-1369806_1686.20EUR.pdf
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