Of rats and men: A translational model to understand vancomycin pharmacokinetic/toxicodynamic relationships

Marc H. Scheetz, Gwendolyn M. Pais, Thomas P. Lodise, Steven Y.C. Tong, Joshua S. Davis, J. Nicholas O'Donnell, Jiajun Liu, Michael Neely, Walter C. Prozialeck, Peter C. Lamar, Nathaniel J. Rhodes, Thomas Holland, Sean N. Avedissian

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Article numbere01060-21
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume65
Issue number10
DOIs
Publication statusPublished - Sept 2021

Bibliographical note

Funding Information:
The animal work conducted was supported in part by National Institute of Allergy and Infectious Diseases under award number R15-AI105742 (M.H.S., G.P., T.P.L., W.C.P., and P.C.L.), and modeling was performed under R21-AI149026 (M.H.S., G.P., W.C.P., and P.C.L.). The PROVIDE study data were supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number UM1AI104681. S.Y.C.T. is supported by an Australian National Health and Medical Research Council Career Development Fellowship (number 1145033).

Funding Information:
M. H. Scheetz has ongoing research contracts with Nevakar and SuperTrans Medical and has filed patent US10688195B2. All other authors have no other related conflicts of interest to declare. The animal work conducted was supported in part by National Institute of Allergy and Infectious Diseases under award number R15-AI105742 (M.H.S., G.P., T.P.L., W.C.P., and P.C.L.), and modeling was performed under R21-AI149026 (M.H.S., G.P., W.C.P., and P.C.L.). The PROVIDE study data were supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number UM1AI104681. S.Y.C.T. is supported by an Australian National Health and Medical Research Council Career Development Fellowship (number 1145033). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. For J.L., this article reflects the views of the author and should not be construed to represent FDA's views or policies.

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