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AUC Versus Peak–Trough Dosing of Vancomycin: Applying New Pharmacokinetic Paradigms to an Old Drug

Brown, Daniel L. PharmD; Lalla, Christina D. PharmD Candidate; Masselink, Andrew J. PharmD Candidate

doi: 10.1097/FTD.0b013e31828b2a50
Review Article

Objectives: To compare and contrast the pharmacokinetic/pharmacodynamic foundations of traditional “peak–trough” vancomycin dosing methods versus newer “area under the curve” (AUC) strategies. To propose a new AUC-based dosing chart for empirically determining an initial vancomycin dosing regimen designed to achieve a desired AUC24 using the minimum inhibitory concentration (MIC), creatinine clearance (CrCl), and vancomycin clearance (ClVanco).

Review of vancomycin dosing: Peak–trough vancomycin dosing is designed to achieve a C peak of 20–40 mg/L and a C trough of 10–15 or 15–20 mg/L, depending on the severity of the infection and the nature of the pathogen. New treatment guidelines for vancomycin suggest that therapy should achieve an AUC24/MIC of ≥400. AUC-based vancomycin dosing derives the daily dose from ClVanco, MIC, and the desired AUC24/MIC, without consideration of the patient’s weight.

New AUC dosing chart: A vancomycin dosing chart is proposed that estimates ClVanco using the following formula developed by Matzke et al: ClVanco in L/h = [(CrClmL/min × 0.689) + 3.66] × 0.06, which simplifies to (CrClmL/min × 0.41) + 0.22. Two levels of dosing are included—high dose (C trough: 15–20 mg/L) and moderate dose (C trough: 10–15 mg/L). Although the chart has not been validated clinically, it represents the product of standard dosing equations that are used to determine a starting dosing regimen based on well-established vancomycin pharmacokinetic parameters.

Conclusions: An understanding of pharmacokinetic and pharmacodynamic principles, including the relevance of AUC in relation to MIC, enables clinicians to make the best use of vancomycin dosing options. The proposed dosing chart is pharmacokinetically valid but has yet to be applied clinically. It provides a foundation for further study of how clinicians can determine an optimal AUC-based starting vancomycin dosing regimen without having to derive ClVanco or AUC24.

Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL.

Correspondence: Daniel L. Brown, PharmD, Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, PO Box 24708, West Palm Beach, FL 33416 (e-mail: daniel_brown@pba.edu).

The authors declare that there are no conflicts of interest or financial interests of any type relating to the information contained in this manuscript, for themselves or immediate family members, including grants, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents, and royalties. This information has been neither presented nor published elsewhere.

Received November 28, 2012

Accepted January 31, 2013

© 2013 by Lippincott Williams & Wilkins