Comparison of the predictive accuracy of the physiologically based pharmacokinetic (PBPK) model and population pharmacokinetic (PPK) model of vancomycin in Japanese patients with MRSA infection

Abstract

IntroductionThe latest therapeutic drug monitoring guidelines for vancomycin (VCM) recommend that area under the concentration-time curve is estimated based on model-informed precision dosing and used to evaluate efficacy and safety. Therefore, we predicted VCM concentrations in individual methicillin-resistant Staphylococcus aureus-infected patients using existing a physiologically based pharmacokinetic (PBPK) model and 1- and 2-compartment population pharmacokinetic (PPK) models and confirmed and verified the accuracy of the PBPK model in estimating VCM concentrations with the PPK model. MethodsThe subjects of the study are 20 patients, and the predicted concentrations were evaluated by comparing the observed and predicted trough and peak values of VCM concentrations for individual patients. ResultsThe results showed good correlation between the observed and predicted trough and peak concentrations of VCM was observed generally in the PBPK model, R2 values of 0.72, 0.62, and 0.40 with trough values of 0.49, 0.40, and 0.34 with peak values for PBPK model, 1-compartment, and 2-compartment model, respectively. ConclusionsAlthough the performance of the PBPK model is not as predictive as the PPK model, generally similar predictive trends were obtained, suggesting that it may be a valuable tool for rapid and accurate prediction of AUC for VCM.