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

doi:10.1128/AAC.01060-21

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.

Authors

Marc H Scheetz^{1

2

3}, Gwendolyn M Pais^{1

2}, Thomas P Lodise⁴, Steven Y C Tong^{5

6

7}, Joshua S Davis⁷, J Nicholas O'Donnell⁴, Jiajun Liu⁸, Michael Neely⁹, Walter C Prozialeck³, Peter C Lamar³, Nathaniel J Rhodes^{1

2}, Thomas Holland^{10

11}, Sean N Avedissian^{12

13}

Affiliations

¹ Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern Universitygrid.260024.2, Downers Grove, Illinois, USA.
² Chicago College of Pharmacy, Center of Pharmacometric Excellence, Midwestern Universitygrid.260024.2, Downers Grove, Illinois, USA.
³ College of Graduate Studies, Department of Pharmacology, Midwestern Universitygrid.260024.2, Downers Grove, Illinois, USA.
⁴ Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciencesgrid.413555.3, Albany, New York, USA.
⁵ Victorian Infectious Diseases Service, Peter Doherty Institute for Infection and Immunity, The Royal Melbourne Hospital, Melbourne, Australia.
⁶ Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
⁷ Menzies School of Health Researchgrid.271089.5, Charles Darwin University, Darwin, Australia.
⁸ Division of Pharmacometrics, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
⁹ Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.
¹⁰ Duke Universitygrid.26009.3d School of Medicine, Durham, North Carolina, USA.
¹¹ Duke Clinical Research Institute, Durham, North Carolina, USA.
¹² Antiviral Pharmacology Laboratory, University of Nebraska Medical Center (UNMC) Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska, USA.
¹³ University of Nebraska Medical Center, College of Pharmacy, Omaha, Nebraska, USA.

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.

Keywords: AKI; CAMERA2; PROVIDE; allometric; biomarkers; glycopeptides; laboratory animals; preclinical; toxicity; vancomycin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acute Kidney Injury* / chemically induced
Acute Kidney Injury* / drug therapy
Animals
Anti-Bacterial Agents / adverse effects
Area Under Curve
Prospective Studies
Rats
Vancomycin* / adverse effects

Substances

Anti-Bacterial Agents
Vancomycin

Abstract

Publication types

MeSH terms

Substances

Grants and funding