Simulation of vancomycin peak and trough concentrations using five dosing methods in 37 patients

Five methods of dosing vancomycin (Matzke, Moellering, Nielsen, Lake-Peterson, and manufacturer's) were simulated in 37 patients. Ten serum samples were obtained after a 1-hour intravenous infusion of 6.2-20 mg/kg total body weight. A preinfusion serum sample was obtained from patients not studied on the first dose. Initial estimates of pharmacokinetic values were made using nonlinear iterative least squares regression and serum concentration-time data. These data were fitted to a two-compartment, open-infusion model. Simulations of the peak and trough serum concentrations at steady state for each patient were determined by multiple-dose simulated pharmacokinetics and each patient's pharmacokinetic values using the regimen suggested by each of the five methods. Steady-state serum concentrations, predicted systemic clearance by each method (except Lake-Peterson), and the daily dose for each patient recommended by each method were determined. All the methods underpredicted actual drug clearance, with the Nielsen method having the lowest prediction. The Matzke method recommended the largest dosage. Using each of the methods, only 3-16% of patients would have achieved recommended peak and trough serum concentrations. In the simulation model used, no method performed satisfactorily in attaining the desired vancomycin peak and trough concentrations. We suggest that the Lake-Peterson method could be used initially, provided that monitoring is also performed to adjust the dosage regimen further.