Comparison of the Area-Under-The-Curve for Vancomycin Estimated Using Compartmental and Non-compartmental Methods in Adult Patients with Normal Renal Function.

AIMS 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 (AUC0-∞) was calculated for each subject using non-compartmental methods (AUCNCA) and by fitting 1- (AUC1CMT), 2- (AUC2CMT), and 3- (AUC3CMT) compartment infusion models. The optimal model fit was determined using the Akaike information criterion and visual inspection of the residual plots. The individual compartmental AUC0-∞ values from the 1- and 2-compartment models were compared with AUCNCA values using one-way repeated measures ANOVA. RESULTS The mean (± standard deviation) AUC estimates were similar for the different methods: AUCNCA 180 ± 86 mg.h/L, AUC1CMT 167 ± 79 mg.h/L, and AUC2CMT 183 ± 88 mg.h/L. Despite the overlapping AUC values, AUC2CMT and AUCNCA were significantly greater than AUC1CMT (P<0.05). The 3-compartment model was excluded from the analysis due to the failure to converge in some instances. CONCLUSIONS Dose prediction software utilizing 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.