Vancomycin Dosing: Assessment of Time to Therapeutic Concentration and Predictive Accuracy of Pharmacokinetic Modeling Software

Abstract

Therapeutic drug monitoring is usually required for safe and effective administration of vancomycin. However, dosing recommendations from published guidelines are not suitable in achieving therapeutic vancomycin concentrations in a timely manner in patients with normal renal function. To audit vancomycin dosing and concentrations at our institution and evaluate the predictive accuracy of a pharmacokinetic simulation program, with a view to implementing a pharmacy-based pharmacokinetic service for vancomycin monitoring. Patients receiving vancomycin were identified prospectively through the therapeutic drug monitoring archives. Patient information was obtained from medication charts and medical records that were located on wards. Data were entered into the MM-USC*Pack program (Jelliffe R, University of Southern California, 2008, version 12.10). This software was used to predict initial and subsequent concentrations of vancomycin based on patient parameters. The predictive accuracy of this software was evaluated by comparing the predicted concentrations to the observed concentrations. During a 6-week period, 204 concentrations were measured in 77 patients. The most common dosing regimen was 1 g every 12 hours. Overall, initial trough concentrations were subtherapeutic (<10 mg/L) in 58% of patients and trough concentrations did not become therapeutic at any stage throughout therapy in 25% of patients. The pharmacokinetic modeling software demonstrated little systematic bias (-3.1%), but the precision (median prediction error) was 23% (interquartile range, 11-45%). Predictions were poorer in obese patients (body mass index >35 kg/m(2)) and in patients with unstable renal function. A delay in attaining target trough concentrations was observed in a significant proportion of patients. Pharmacokinetic modeling software is a potential tool to improve the timeliness of achieving adequate dosing by allowing concentrations to be determined prior to steady-state. The program was able to predict vancomycin concentrations across a heterogeneous patient population with little systematic bias, but only moderate precision.