Of Rats and Men: a Translational Model To Understand Vancomycin Pharmacokinetic/Toxicodynamic Relationships.

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Issue Date
9/17/2021
Authors
Scheetz, Marc H
Pais, Gwendolyn M
Lodise, Thomas P
Tong, Steven Y C
Davis, Joshua S
O'Donnell, J Nicholas
Liu, Jiajun
Neely, Michael N
Prozialeck, Walter C
Lamar, Peter C
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Abstract
Vancomycin area under the concentration curve (AUC) is known to predict vancomycin-induced acute kidney injury (AKI). Data were analyzed from a rat model (n = 48) and two prospective clinical studies (PROVIDE [n = 263] and CAMERA2 [n = 291]). A logit-link model was used to calculate the multiplicative factors between the probability of AKI from clinical studies and in the rat. The rat was 2.7 to 4.2 times more sensitive to AKI between AUCs of 199.5 and 794.3 mg.h/liter, respectively.
Citation
Scheetz MH, Pais GM, Lodise TP, Tong SYC, Davis JS, O'Donnell JN, Liu J, Neely M, Prozialeck WC, Lamar PC, Rhodes NJ, Holland T, Avedissian SN. Of Rats and Men: a Translational Model To Understand Vancomycin Pharmacokinetic/Toxicodynamic Relationships. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0106021. doi: 10.1128/AAC.01060-21. Epub 2021 Aug 2. PMID: 34339278; PMCID: PMC8448150.
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Grants
R21 AI149026/AI/NIAID NIH HHS/United States , 1145033/Australian National Health and Medical Research Council Career , Development Fellowship , UM1 AI104681/AI/NIAID NIH HHS/United States , UM1AI104681/HHS | National Institutes of Health (NIH) , R21-AI149026/HHS | National Institutes of Health (NIH) , R15-AI105742/HHS | National Institutes of Health (NIH) , R15 AI105742/AI/NIAID NIH HHS/United States