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230 results on '"Liebchen, Uwe"'

9. Towards model-informed precision dosing of piperacillin: multicenter systematic external evaluation of pharmacokinetic models in critically ill adults with a focus on Bayesian forecasting

Author

Greppmair, Sebastian, Brinkmann, Alexander, Roehr, Anka, Frey, Otto, Hagel, Stefan, Dorn, Christoph, Marsot, Amélie, El-Haffaf, Ibrahim, Zoller, Michael, Saller, Thomas, Zander, Johannes, Schatz, Lea Marie, Scharf, Christina, Briegel, Josef, Minichmayr, Iris K., Wicha, Sebastian G., and Liebchen, Uwe

Published
2023
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12. Ecological effects of selective oral decontamination on multidrug-resistance bacteria acquired in the intensive care unit: a case–control study over 5 years

Author

Wang, Boacheng, Briegel, Josef, Krueger, Wolfgang A., Draenert, Rika, Jung, Jette, Weber, Alexandra, Bogner, Johannes, Schubert, Sören, Liebchen, Uwe, Frank, Sandra, Zoller, Michael, Irlbeck, Michael, Ney, Ludwig, Weig, Thomas, Hinske, Ludiwg, Niedermayer, Sebastian, Kilger, Erich, Möhnle, Patrick, and Grabein, Beatrice

Published
2022
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17. Therapeutic Drug Monitoring of Elexacaftor, Tezacaftor, and Ivacaftor in Adult People with Cystic Fibrosis.

Author

Naehrig, Susanne, Shad, Christina, Breuling, Magdalena, Goetschke, Melanie, Habler, Katharina, Sieber, Sarah, Kastenberger, Johanna, Kunzelmann, Alexandra Katharina, Sommerburg, Olaf, Liebchen, Uwe, Behr, Juergen, Vogeser, Michael, and Paal, Michael

Subjects
DRUG monitoring, CYSTIC fibrosis, PRODUCT attributes, PHARMACOKINETICS, BLOOD sampling
Abstract

Background/Objectives: Elexacaftor, tezacaftor, and ivacaftor (ETI) have significantly improved lung function in people with cystic fibrosis (pwCF). Despite exceptional improvements in most cases, treatment-related inter-subject variability and drug–drug interactions that complicate modulator therapy have been reported. Methods: This retrospective analysis presents data on the serum concentration of ETI in our pwCF with full or reduced dosage from August 2021 to December 2023 via routine therapeutic drug monitoring (TDM). The data were compared with the maximum drug concentrations (Cmax) from the pharmaceutical company's summary of product characteristics. Results: A total of 786 blood samples from 155 pwCF (41% female, 59% male) were analyzed. The examinations were divided into four groups: full dose within the given tmax (38.5% of all measurements), full dose outside the tmax (29%), reduced dose within the tmax (19.2%), and reduced dose outside the tmax (13.2%). In pwCF receiving the full dose and blood taken within the tmax, 45.3% of serum concentrations of elexacaftor, 51.1% of serum concentrations of ivacaftor, and 8.9% of serum concentrations of tezacaftor were found to be above the Cmax, respectively. For those on reduced doses within the tmax, 24.5% had a serum concentration of elexacaftor, 23.2% had a serum concentration of ivacaftor, and 2.5% had a serum concentration of tezacaftor above the Cmax, respectively. Conclusions: Many pwCF under ETI therapy have Cmax values for elexacaftor and ivacaftor above the recommended range, even on reduced doses or before the tmax was reached. This highlights the value of a TDM program. Further pharmacokinetic studies are necessary. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Extracorporeal Elimination of Pro- and Anti-inflammatory Modulators by the Cytokine Adsorber CytoSorb®in Patients with Hyperinflammation: A Prospective Study

Author

Graf, Helen, Gräfe, Caroline, Bruegel, Mathias, Happich, Felix L., Wustrow, Vassilissa, Wegener, Aljoscha, Wilfert, Wolfgang, Zoller, Michael, Liebchen, Uwe, Paal, Michael, and Scharf, Christina

Abstract

Introduction: The release of pro-inflammatory cytokines in critically ill patients with sepsis leads to endothelial dysfunction resulting in cardiocirculatory insufficiency. Their extracorporeal elimination using the cytokine adsorber CytoSorb®(CS) (adsorption of especially hydrophobic molecules < 60 kDa) might be promising, but data about the adsorption capacity as well as a potential harmful adsorption of anti-inflammatory cytokines are missing so far. Methods: The prospective Cyto-SOLVE-study included 15 patients with sepsis or other hyperinflammatory conditions (interleukin 6 > 500 pg/ml), continuous kidney replacement therapy, and the application of CS. Various cytokines and chemokines were measured pre- and post-CS as well as in patients’ blood at predefined timepoints. Significant changes in the concentrations were detected with the Wilcoxon test with associated samples. Clearance of the adsorber (ml/min) was calculated with: bloodflow∗concentrationpre-postconcentrationpre.\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$blood\,flow*\frac{{concentration\, \left( {pre - post} \right)}}{{concentration\, \left( {pre} \right)}}.$$\end{document} Results: Most of the inflammatory mediators showed a high initial extracorporeal clearance of 70–100 ml/min after CS installation, which dropped quickly to 10-30 ml/min after 6 h of treatment. No difference in clearance was observed between pro- and anti-inflammatory cytokines. Despite extracorporeal adsorption, a significant (p< 0.05) decrease in the blood concentration after 6 h was only observed for the pro-inflammatory cytokines tumor necrosis factorα (TNF-α) (median 284 vs. 230 pg/ml), vascular endothelial growth factor (VEGF) (median 294 vs. 252 pg/ml), macrophage inflammatory protein 1a (MIP-1a) (median 11.1 vs. 9.0 pg/ml), and regulated upon activation, normal T cell expressed and secreted (RANTES) (median 811 vs. 487 pg/ml) as well as the anti-inflammatory cytokines interleukin 4 (median 9.3 vs. 6.4 pg/ml), interleukin 10 (median 88 vs. 56 pg/ml), and platelet-derived growth factor (PDGF) (median 177 vs. 104 pg/ml). A significant (p< 0.05) decrease in patients’ blood after 12 h was only detected for interleukin 10. Conclusions: CS can adsorb pro- as well as anti-inflammatory mediators with no relevant difference regarding the adsorption rate. A fast saturation of the adsorber resulted in a rapid decrease of the clearance. The potential clinical benefit or harm of this unspecific cytokine adsorption needs to be evaluated in the future. Trial Registration: ClinicalTrials.gov NCT04913298, registration date June 4, 2021.

Published
2024
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35. Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Vancomycin in Patients with External Ventricular Drain

Author

Chen, Zhendong, primary, Taubert, Max, additional, Chen, Chunli, additional, Dokos, Charalambos, additional, Fuhr, Uwe, additional, Weig, Thomas, additional, Zoller, Michael, additional, Heck, Suzette, additional, Dimitriadis, Konstantinos, additional, Terpolilli, Nicole, additional, Kinast, Christina, additional, Scharf, Christina, additional, Lier, Constantin, additional, Dorn, Christoph, additional, and Liebchen, Uwe, additional

Published
2023
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37. Systematic Evaluation of Pharmacokinetic Models for Model-Informed Precision Dosing of Meropenem in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy

Author

Schatz, Lea Marie, primary, Brinkmann, Alexander, additional, Röhr, Anka, additional, Frey, Otto, additional, Greppmair, Sebastian, additional, Weinelt, Ferdinand, additional, Zoller, Michael, additional, Scharf, Christina, additional, Hempel, Georg, additional, and Liebchen, Uwe, additional

Published
2023
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38. Correlation between Bilirubin Elimination with the Cytokine Adsorber CytoSorb® and Mortality in Critically Ill Patients with Hyperbilirubinemia.

Author

Gräfe, Caroline, Paal, Michael, Winkels, Martin, Irlbeck, Michael, Liebchen, Uwe, and Scharf, Christina

Subjects
BILIRUBIN, CRITICALLY ill, RENAL replacement therapy, INTENSIVE care patients, HYPERBILIRUBINEMIA
Abstract

Introduction: Hyperbilirubinemia is often the first evidence for any kind of liver disorder and over one-third of all patients in intensive care units (ICU) show elevated bilirubin concentrations. In critically ill patients, high concentrations of serum bilirubin are correlated with a poor outcome. Therapies to lower bilirubin concentrations are often just symptomatically and their effect on the patients' outcome is hardly evaluated. Therefore, this study investigates whether the extracorporeal elimination of bilirubin with the cytokine adsorber CytoSorb® (CS) reduces mortality in patients with hyperbilirubinemia. Methods: Patients with bilirubin concentrations >10 mg/dL at the ICU were screened for evaluation from 2018 to 2020. Patients with kidney replacement therapy and older than 18 years were included. Patients with continuously decreasing bilirubin concentrations after liver transplantation or other liver support systems (i.e., Molecular Adsorbents Recirculating System [MARS®], Advanced Organ Support [ADVOS]) were excluded. CS therapy was used in clinical routine and was indicated by the treating physicians. Statistical analysis was performed with IBM SPSS statistics utilizing a multivariate model. Primary outcome measure was the effect of CS on the 30-day mortality. Results: Data from 82 patients (mean Simplified Acute Physiology Score [SAPS] II: 74 points, mean bilirubin: 18 mg/dL, mean lactate: 3.7 mmol/L) were analyzed. There were no significant differences in patients with and without CS treatment. The multivariate model showed no significant effect of CS therapy (p = 0.402) on the 30-day mortality. In addition, a significant effect of bilirubin concentration (p = 0.274) or Model for End-Stage Liver Disease score (p = 0.928) on the 30-day mortality could not be shown. In contrast, lactate concentration (p = 0.001, b = 0.044) and SAPS II (p = 0.025, b = 0.008) had significant impact on 30-day mortality. Conclusion: The use of CS in patients with hyperbilirubinemia did not result in a significant reduction in 30-day mortality. Randomized and controlled studies with mortality as primary outcome measure are needed in the future to justify their use. [ABSTRACT FROM AUTHOR]

Published
2023
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41. No clinically relevant removal of meropenem by cytokine adsorber CytoSorb.sup.® in critically ill patients with sepsis or septic shock

Author

Liebchen, Uwe, Scharf, Christina, Zoller, Michael, Weinelt, Ferdinand, Kloft, Charlotte, Michelet, Robin, and Schroeder, Ines

Subjects
Cytokines, Infection, Septic shock, Health care industry
Abstract

Author(s): Uwe Liebchen [sup.1] [sup.2], Christina Scharf [sup.1], Michael Zoller [sup.1], Ferdinand Weinelt [sup.2] [sup.3], Charlotte Kloft [sup.2], Robin Michelet [sup.2], Ines Schroeder [sup.1], Michael Paal [sup.4], Michael Vogeser [sup.4], [...]

Published
2021
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49. Target Site Pharmacokinetics of Meropenem: Measurement in Human Explanted Lung Tissue by Bronchoalveolar Lavage, Microdialysis, and Homogenized Lung Tissue

Author

Paal, Michael, primary, Scharf, Christina, additional, Denninger, Ann Katrin, additional, Ilia, Luis, additional, Kloft, Charlotte, additional, Kneidinger, Nikolaus, additional, Liebchen, Uwe, additional, Michel, Sebastian, additional, Schneider, Christian, additional, Schröpf, Sebastian, additional, Schuster, Carina, additional, Vogeser, Michael, additional, Weinelt, Ferdinand, additional, Zander, Johannes, additional, Zoller, Michael, additional, and Schroeder, Ines, additional

Published
2021
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