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@ARTICLE{Sundheimer:300695,
author = {J. K. Sundheimer$^*$ and J. Benzel$^*$ and R.
Longuespée$^*$ and J. Burhenne and S. Pfister$^*$ and K.
Maass$^*$ and M. Sauter and K. Pajtler$^*$},
title = {{E}xperimental {I}nsights and {R}ecommendations for
{S}uccessfully {P}erforming {C}erebral {M}icrodialysis
{W}ith {H}ydrophobic {D}rug {C}andidates.},
journal = {Clinical and translational science},
volume = {18},
number = {5},
issn = {1752-8054},
address = {Oxford},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2025-00875},
pages = {e70226},
year = {2025},
note = {#EA:B062#LA:B062#},
abstract = {Cerebral 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.},
subtyp = {Review Article},
keywords = {Microdialysis: methods / Microdialysis: instrumentation /
Animals / Blood-Brain Barrier: metabolism / Hydrophobic and
Hydrophilic Interactions / Brain: metabolism /
Reproducibility of Results / Rats / Humans / Mice / central
nervous system (Other) / cerebral microdialysis (Other) /
chemical drug properties (Other) / non‐specific binding
(Other) / probe implantation (Other)},
cin = {B062 / HD01 / B350},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B350-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40286321},
pmc = {pmc:PMC12033007},
doi = {10.1111/cts.70226},
url = {https://inrepo02.dkfz.de/record/300695},
}