TY  - JOUR
AU  - Sundheimer, Julia K
AU  - Benzel, Julia
AU  - Longuespée, Rémi
AU  - Burhenne, Jürgen
AU  - Pfister, Stefan
AU  - Maass, Kendra
AU  - Sauter, Max
AU  - Pajtler, Kristian
TI  - Experimental Insights and Recommendations for Successfully Performing Cerebral Microdialysis With Hydrophobic Drug Candidates.
JO  - Clinical and translational science
VL  - 18
IS  - 5
SN  - 1752-8054
CY  - Oxford
PB  - Wiley-Blackwell
M1  - DKFZ-2025-00875
SP  - e70226
PY  - 2025
N1  - #EA:B062#LA:B062# 
AB  - 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.
KW  - Microdialysis: methods
KW  - Microdialysis: instrumentation
KW  - Animals
KW  - Blood-Brain Barrier: metabolism
KW  - Hydrophobic and Hydrophilic Interactions
KW  - Brain: metabolism
KW  - Reproducibility of Results
KW  - Rats
KW  - Humans
KW  - Mice
KW  - central nervous system (Other)
KW  - cerebral microdialysis (Other)
KW  - chemical drug properties (Other)
KW  - non‐specific binding (Other)
KW  - probe implantation (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40286321
C2  - pmc:PMC12033007
DO  - DOI:10.1111/cts.70226
UR  - https://inrepo02.dkfz.de/record/300695
ER  -