Comparison of the Area Under the Curve for Vancomycin Estimated Using Compartmental and Noncompartmental Methods in Adult Patients With Normal Renal Function

Ther Drug Monit. 2019 Dec;41(6):726-731. doi: 10.1097/FTD.0000000000000690.


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 (AUC0-∞) was calculated for each subject using noncompartmental 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 analysis of variance.

Results: The mean (±SD) 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 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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Anti-Bacterial Agents / blood*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Humans
  • Reproducibility of Results
  • Vancomycin / blood*
  • Vancomycin / pharmacokinetics*


  • Anti-Bacterial Agents
  • Vancomycin