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SHR Neuro Cancer Cardio Lipid Metab Microb

Altendorfer-Kroath, T; Schimek, D; Eberl, A; Rauter, G; Ratzer, M; Raml, R; Sinner, F; Birngruber, T.
Comparison of cerebral Open Flow Microperfusion and Microdialysis when sampling small lipophilic and small hydrophilic substances.
J Neurosci Methods. 2019; 311(4):394-401 Doi: 10.1016/j.jneumeth.2018.09.024
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Leading authors Med Uni Graz: Birngruber Thomas
Co-authors Med Uni Graz: Rauter Günther; Sinner Frank Michael
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Abstract:: Assessment of drug concentration in the brain interstitial fluid (ISF) is crucial for development of brain active drugs, which are mainly small, lipophilic substances able to cross the blood-brain barrier (BBB). We aimed to compare the applicability of cerebral Open Flow Microperfusion (cOFM) and Microdialysis (MD) to sample the lipophilic substance amitriptyline (AMI), its metabolites Hydroxyamitriptyline (HYA), Nortriptyline (NOR), Amitriptyline-N-Oxide (ANO), deuterated water (D₂O) and the hydrophilic substance sodium fluorescein (Naf) in brain ISF. NEW METHOD: cOFM has been refined to yield increased spatial resolution and performance. Performance of cOFM and MD was assessed by in vivo AUC ratios of probe samples (AUC_COFM/AUC_MD) and the in vivo relative recovery of D₂O (RR_vv,D2O). Adsorption of AMI and Naf to MD and cOFM was assessed by the in vitro relative recovery (RR_vt) prior to the in vivo experiments. The in vivo AUC ratio of AMI and RR_vv,D2O was about two times higher for cOFM than for MD (AUC_OFM/AUC_MD = 2.0, RR_vv,D2O(cOFM)/RR_vv,D2O(MD) = 2.1). cOFM detected all investigated AMI metabolites except NOR. MD did not detect HYA, NOR, ANO and Naf. In vitro adsorption of AMI and Naf to the MD membrane was strong (RR_vt,AMI = 4.4%, RR_vt,Naf = 1.5%) but unspecific adsorption to cOFM was negligibly small (RR_vt,AMI = 98% and RR_vt,Naf = 98%). cOFM showed better performance when sampling AMI and its metabolites, Naf and D₂O, and had an about two times higher RR_vv,D2O than MD. MD did not detect HYA, NOR, ANO and Naf, most likely due to membrane adsorption. Copyright © 2018. Published by Elsevier B.V.
Find related publications in this database (using NLM MeSH Indexing): Amitriptyline - administration & dosage; Amitriptyline - analysis; Amitriptyline - metabolism; Animals -; Brain Chemistry -; Extracellular Fluid - chemistry; Male -; Microdialysis - methods; Perfusion - methods; Rats, Sprague-Dawley -
Find related publications in this database (Keywords): Cerebral open flow microperfusion; cOFM; Microdialysis; Small lipophilic substances; Blood brain barrier; Brain interstitial fluid; Brain active drugs