Comparison Of The Area Under The Curve For Vancomycin Estimated Using Compartmental And Noncompartmental Methods In Adult Patients With Normal Renal Function

Background: Vancomycin pharmacokinetics are best described using a 2-compartment model. However, 1-compartment population models are commonly used as the basis for dose prediction software. Therefore, the validity of using a 1-compartment model to guide vancomycin drug dosing was examined.Methods: Published plasma concentration-time data from adult subjects (n = 30) with stable renal function administered a single intravenous infusion of vancomycin were extracted from previous studies. The vancomycin area under the curve (AUC(0-infinity)) was calculated for each subject using noncompartmental methods (AUC(N-CA)) and by fitting 1- (AUC(1CMT)), 2- (AUC(2CMT)), and 3- (AUC(3CMT)) compartment infusion models. The optimal model fit was determined using the Akaike information criterion and visual inspection of the residual plots. The individual compartmental AUC(0-infinity) values from the 1- and 2-compartment models were compared with AUC(NCA) values using one-way repeated measures analysis of variance.Results: The mean (+/- SD) AUC estimates were similar for the different methods: AUC(NCA) 180 +/- 86 mg.h/L, AUC(1CMT) 167 +/- 79 mg.h/L, and AUC(2CMT) 183 +/- 88 mg.h/L. Despite the overlapping AUC values, AUC(2CMT) and AUC(NCA) were significantly greater than AUC(1CMT) (P < 0.05). The 3-compartment model was excluded from the analysis because of the failure to converge in some instances.Conclusions: Dose prediction software using a 1-compartment model as the basis for Bayesian forecasting underestimates drug exposure (estimated as the AUC) by less than 10%. This is unlikely to be clinically significant with respect to dose adjustment. Therefore, a 1-compartment model may be sufficient to guide vancomycin dosing in adult patients with stable renal function.