Dosing methods proposed by Matzke et al., Moellering et al., and Lake and Peterson were used to predict initial doses of vancomycin for serum concentration simulation using a two-compartment open model. Previously reported pharmacokinetic data from 25 of 28 patients were used to simulate steady-state serum vancomycin concentrations for doses derived from the three methods. The Matzke method failed to provide simulated one-hour postinfusion levels < 30 μg/mL in 48 percent and troughs > 5 μg/mL in more than 88 percent of the patients. The Moellering method succeeded in achieving this goal in 96 percent of the simulated one-hour levels, and in 72 percent of the troughs when a six-hour dosing interval was selected. For the 8 mg/kg Lake-Peterson doses, one-hour levels > 30 μg/mL occurred in 28 percent of the simulations, and for the 10 mg/kg doses this increased to 40 percent. The 8 mg/kg doses resulted in trough simulations < 5 μg/mL in 28 percent and the 10 mg/kg reduced this to only 20 percent. These simulations indicated that the Moellering nomogram with the six-hour dosing interval was the most successful method for initial dose selection, but early serum concentration monitoring and adjustment of initial empirical and nomogram-derived doses is necessary to assure safe and effective vancomycin serum concentrations.
A model system for investigating the biliary excretion of an anion in the rat