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Open Access 16-11-2023 | Vancomycin | Original Research Article

How to Dose Vancomycin in Overweight and Obese Patients with Varying Renal (Dys)function in the Novel Era of AUC 400–600 mg·h/L-Targeted Dosing

Authors: Tan Zhang, Elke H. J. Krekels, Cornelis Smit, Eric P. A. van Dongen, Roger J. M. Brüggemann, Catherijne A. J. Knibbe

Published in: Clinical Pharmacokinetics | Issue 1/2024

Abstract

Background and Objective

The latest vancomycin guideline recommends area under the curve (AUC)-targeted dosing and monitoring for efficacy and safety. However, guidelines for AUC-targeted starting dosing in patients with obesity and/or renal insufficiency are currently lacking. This study quantifies the pharmacokinetics (PK) of vancomycin in this population and provides AUC-targeted dosing recommendations.

Methods

Vancomycin concentrations (n = 1188) from therapeutic drug monitoring of 210 overweight and obese patients with varying degrees of renal (dys)function from the ward (74.8%) and intensive care unit (ICU, 25.2%) were pooled with published rich concentration–time data (n = 207) from 20 (morbidly) obese subjects undergoing bariatric surgery. A population model was developed using NONMEM 7.4. Stochastic simulations were performed to design dosing guidelines targeting an AUC₂₄ between 400–600 mg·h/L.

Results

Vancomycin clearance (CL) was found to increase linearly with total bodyweight and with renal function (CKD-EPI) in a power relation. Additionally, CL proved 15.5% lower in ICU patients. Our model shows that, to reach the target AUC between 400 and 600 mg·h/L in the first 48 h, two loading doses are required for both continuous infusion and intermittent dosing regimens. Maintenance doses were found to require adjustment for total bodyweight, renal function, and ICU admission status. With this guideline, the median AUC₂₄ is well within the target from the start of the treatment onwards.

Conclusions

To achieve safe and effective vancomycin exposure for maintenance doses in overweight and obese patients, renal function, total bodyweight, and ICU admission status should be taken into account.

Trial Registration

The AMIGO trial was registered in the Dutch Trial Registry [NTR6058].

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Title: How to Dose Vancomycin in Overweight and Obese Patients with Varying Renal (Dys)function in the Novel Era of AUC 400–600 mg·h/L-Targeted Dosing
Authors: Tan Zhang
Elke H. J. Krekels
Cornelis Smit
Eric P. A. van Dongen
Roger J. M. Brüggemann
Catherijne A. J. Knibbe
Publication date: 16-11-2023
Publisher: Springer International Publishing
Keywords: Vancomycin
Overweight
Pharmacokinetics
Published in: Clinical Pharmacokinetics / Issue 1/2024
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-023-01324-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

How to Dose Vancomycin in Overweight and Obese Patients with Varying Renal (Dys)function in the Novel Era of AUC 400–600 mg·h/L-Targeted Dosing

Abstract

Background and Objective

Methods

Results

Conclusions

Trial Registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and Objective

Methods

Results

Conclusions

Trial Registration

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