Impact of humanized vancomycin infusion on kidney function and kidney injury in a translational rat model
Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved..
Allometric dose scaling aims to create isometric exposures between animals and humans and is often employed in preclinical pharmacokinetic/pharmacodynamic models. Bolus-administration with allometric scaling is the most simple and commonly used strategy in pre-clinical kidney injury studies; however, it is possible to humanize drug exposures. Currently, it is unknown if dose-matched, bolus-administration with allometric scaling results in similar outcomes compared to humanized infusions in the vancomycin induced kidney injury model. We utilized a preclinical Sprague-Dawley rat model to compare traditional allometrically-scaled, dose-matched, bolus-administration of vancomycin to an infusion-pump controlled, humanized infusion scheme to assess for differences in iohexol-measured kidney function and urinary kidney injury biomarkers. Following 24 h of vancomycin administration, rats in the humanized infusion group had equivalent area under the curve exposures to animals in the dose-matched bolus group (93.7 mg·h/L [IQR 90.2-97.2] vs. 99.5 mg·h/L [IQR 95.1-104.0], P = 0.07). No significant differences in iohexol-measured kidney function nor meaningful differences in urinary kidney injury biomarkers, kidney injury molecule-1, clusterin, and osteopontin, were detected. Administration of intravenous vancomycin as either a humanized infusion or dose-matched bolus resulted in similar vancomycin exposures. No differences in iohexol-measured GFR nor meaningful differences in urinary kidney injury biomarkers were observed among male Sprague-Dawley rats.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
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| Enthalten in: |
International journal of antimicrobial agents - 63(2024), 5 vom: 15. Apr., Seite 107118 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chang, Jack [VerfasserIn] |
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| Links: |
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| Themen: |
4419T9MX03 |
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| Anmerkungen: |
Date Completed 30.04.2024 Date Revised 30.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijantimicag.2024.107118 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369076222 |
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| 520 | |a Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved. | ||
| 520 | |a Allometric dose scaling aims to create isometric exposures between animals and humans and is often employed in preclinical pharmacokinetic/pharmacodynamic models. Bolus-administration with allometric scaling is the most simple and commonly used strategy in pre-clinical kidney injury studies; however, it is possible to humanize drug exposures. Currently, it is unknown if dose-matched, bolus-administration with allometric scaling results in similar outcomes compared to humanized infusions in the vancomycin induced kidney injury model. We utilized a preclinical Sprague-Dawley rat model to compare traditional allometrically-scaled, dose-matched, bolus-administration of vancomycin to an infusion-pump controlled, humanized infusion scheme to assess for differences in iohexol-measured kidney function and urinary kidney injury biomarkers. Following 24 h of vancomycin administration, rats in the humanized infusion group had equivalent area under the curve exposures to animals in the dose-matched bolus group (93.7 mg·h/L [IQR 90.2-97.2] vs. 99.5 mg·h/L [IQR 95.1-104.0], P = 0.07). No significant differences in iohexol-measured kidney function nor meaningful differences in urinary kidney injury biomarkers, kidney injury molecule-1, clusterin, and osteopontin, were detected. Administration of intravenous vancomycin as either a humanized infusion or dose-matched bolus resulted in similar vancomycin exposures. No differences in iohexol-measured GFR nor meaningful differences in urinary kidney injury biomarkers were observed among male Sprague-Dawley rats | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Kidney injury | |
| 650 | 4 | |a Vancomycin | |
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| 700 | 1 | |a Jubrail, Raymond |e verfasserin |4 aut | |
| 700 | 1 | |a Engel, Patti L |e verfasserin |4 aut | |
| 700 | 1 | |a Scheetz, Marc H |e verfasserin |4 aut | |
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