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000300695 1001_ $$00009-0005-9296-8098$$aSundheimer, Julia K$$b0$$eFirst author
000300695 245__ $$aExperimental Insights and Recommendations for Successfully Performing Cerebral Microdialysis With Hydrophobic Drug Candidates.
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000300695 520__ $$aCerebral microdialysis in rodents represents a robust and versatile technique for quantifying the pharmacologically relevant unbound fraction of drugs in the brain. When this unbound fraction is simultaneously determined in plasma, it facilitates the calculation of the corresponding unbound plasma-to-brain partition coefficient (Kp,uu) for a given compound in vivo. This coefficient is critical for understanding the penetration and distribution of drugs across the blood-brain barrier (BBB). However, obtaining valid and accurate microdialysis data can be particularly challenging for hydrophobic drugs due to their pronounced non-specific interactions with the components of the microdialysis system. The present study reports the outcomes of comprehensive microdialysis investigations in rodents, focusing on three hydrophobic compounds: actinomycin D, selinexor, and ulixertinib. These compounds exhibited varying degrees of non-specific binding to the surfaces of the microdialysis apparatus, leading to low recovery rates and substantial carry-over effects. To diminish these limitations, strategies such as surface coating and the use of optimized materials were employed to enhance the reliability of the microdialysis system. To ensure the robustness and reproducibility of microdialysis-related research outcomes, our experimental findings were supplemented with a narrative literature review. This review encompassed keyword-driven PubMed-indexed publications on microdialysis from 1970 to 2024, providing a broader context for the challenges and solutions associated with the technique. By integrating empirical results with practical recommendations, this study offers a comprehensive resource aimed at advancing the application of cerebral microdialysis in preclinical drug development, particularly for compounds with challenging physicochemical properties.
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000300695 650_7 $$2Other$$acentral nervous system
000300695 650_7 $$2Other$$acerebral microdialysis
000300695 650_7 $$2Other$$achemical drug properties
000300695 650_7 $$2Other$$anon‐specific binding
000300695 650_7 $$2Other$$aprobe implantation
000300695 650_2 $$2MeSH$$aMicrodialysis: methods
000300695 650_2 $$2MeSH$$aMicrodialysis: instrumentation
000300695 650_2 $$2MeSH$$aAnimals
000300695 650_2 $$2MeSH$$aBlood-Brain Barrier: metabolism
000300695 650_2 $$2MeSH$$aHydrophobic and Hydrophilic Interactions
000300695 650_2 $$2MeSH$$aBrain: metabolism
000300695 650_2 $$2MeSH$$aReproducibility of Results
000300695 650_2 $$2MeSH$$aRats
000300695 650_2 $$2MeSH$$aHumans
000300695 650_2 $$2MeSH$$aMice
000300695 7001_ $$0P:(DE-He78)2b12a7cfc604eb9816670e995f7af508$$aBenzel, Julia$$b1$$eFirst author
000300695 7001_ $$0P:(DE-He78)69f4086396e9a4830b9bdb751b68f2a6$$aLonguespée, Rémi$$b2$$udkfz
000300695 7001_ $$00000-0002-2190-1698$$aBurhenne, Jürgen$$b3
000300695 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b4$$udkfz
000300695 7001_ $$0P:(DE-He78)5100059e746b377e2e0a37c0e24f6bf7$$aMaass, Kendra$$b5$$udkfz
000300695 7001_ $$aSauter, Max$$b6
000300695 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian$$b7$$eLast author$$udkfz
000300695 773__ $$0PERI:(DE-600)2433157-0$$a10.1111/cts.70226$$gVol. 18, no. 5, p. e70226$$n5$$pe70226$$tClinical and translational science$$v18$$x1752-8054$$y2025
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