Correlation of Calculated Vancomycin Trough Concentrations and Exposure: A Monte Carlo Simulation

Abstract

Background: Current recommendations are to dose vancomycin to target 24-hour area under the curve (AUC) of 400-600 mg·h/L to optimize efficacy and safety. Limited data support AUC monitoring, and some centers continue to use trough concentrations. A target of 10-20 mg/L has been proposed to reduce nephrotoxicity risk.

Objective: To use previously published pharmacokinetic equations in a Monte Carlo simulation relating AUC exposure to trough concentrations when targeting an AUC between 400 and 600 mg·h/L.

Methods: Previously published pharmacokinetic data were used as input parameters for a Monte Carlo simulation using previously published formulae to correlate AUC to simulated trough concentrations. Pharmacokinetic parameters were assumed to occur in a normal distribution pattern. We excluded irrelevant simulated cases. Maintenance doses of 15 mg/kg were rounded to the nearest 250 mg. Calculated trough concentrations for AUCs of both 400 and 600 mg·h/L were evaluated in each simulation.

Results: A total of 10 000 Monte Carlo simulations were performed. Targeting an AUC of 400 mg·h/L resulted in a mean trough concentration of 10.3 ± 0.8 mg/L. Targeting an AUC of 600 mg·h/L resulted in a mean trough concentration of 15.4 ± 1.2 mg/L.

Conclusion and relevance: We demonstrate that a lower trough concentration range may be supported by an AUC of 400-600 mg·h/L, which may reduce risk and rates of nephrotoxicity without compromising previously established efficacious target trough concentrations.

Keywords: MRSA; drug therapeutic monitoring; glycopeptide; pharmacokinetics; vancomycin.