Quantitative analysis of human brain microdialysate for target site pharmacokinetics of major anesthetics ketamine, midazolam and propofol.

Autor: Guntner AS; Institute of Analytical Chemistry, Johannes Kepler University Linz, Linz, Austria., Buchberger W; Institute of Analytical Chemistry, Johannes Kepler University Linz, Linz, Austria., Hosmann A; Department of Neurosurgery, Medical University Vienna, Vienna, Austria., Mercea PA; Department of Neurosurgery, Medical University Vienna, Vienna, Austria., Koren J; Department of Neurology, Clinic Hietzing, Vienna, Austria; Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology, Vienna, Austria., Reinprecht A; Department of Neurosurgery, Medical University Vienna, Vienna, Austria., Zeitlinger M; Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology, Vienna, Austria; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria., Herta J; Department of Neurosurgery, Medical University Vienna, Vienna, Austria. Electronic address: johannes.herta@meduniwien.ac.at.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2021 Oct 25; Vol. 205, pp. 114289. Date of Electronic Publication: 2021 Jul 29.
DOI: 10.1016/j.jpba.2021.114289
Abstrakt: Brain microdialysis samples of intensive care patients treated with the essential anesthetics ketamine, midazolam and propofol were investigated. Importantly, despite decades of clinical use, comprehensive human cerebral pharmacokinetic data of these drugs is still missing. To encounter this apparent lack of knowledge, we combined cerebral microdialysis with leading-edge analytical instrumentation to monitor the neurochemistry of living human patients. For the quantitative analysis, high performing analytical approaches were developed that can handle minute sample volumes and possible ultralow target analyte levels. The developed methods provided detection limits below 100 ng L -1 for all target analytes and high precision (below 4% RSD intraday). Methods were linear between LODs and 100 μg L -1 for ketamine, 75 μg L -1 for midazolam and 10 μg L -1 for propofol respectively, with coefficients of determination R 2 ≥ 0.999. Further, being aware of the error-prone and demanding translation of microdialysis levels to interstitial concentrations, in vitro approaches for recovery testing of microdialysis probes as well as internal normalization approaches were conducted. Thus, we herein report the first cerebral pharmacokinetic data of ketamine, midazolam and propofol determined in microdialysis samples of 15 neurointensive care patients. We could prove blood-brain barrier penetration of all of the investigated anesthetics and could correlate applied dosages and actual brain exposition of ketamine. However, we emphasize the need of an expanded prospective study including individual microdialysis recovery testing as well as matched serum and/or cerebrospinal fluid collection for a more comprehensive cerebral pharmacokinetic understanding.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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