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

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 AUC(24) using the minimum inhibitory concentration (MIC), creatinine clearance (CrCl), and vancomycin clearance (Cl-Vanco).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 AUC(24)/MIC of 400. AUC-based vancomycin dosing derives the daily dose from Cl-Vanco, MIC, and the desired AUC(24)/MIC, without consideration of the patient's weight.New AUC dosing chart: A vancomycin dosing chart is proposed that estimates Cl-Vanco using the following formula developed by Matzke et al: Cl-Vanco in L/h = [(CrClmL/min x 0.689) + 3.66] x 0.06, which simplifies to (CrClmL/min x 0.41) + 0.22. Two levels of dosing are includedhigh 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 Cl-Vanco or AUC(24).