Development and external validation of a population pharmacokinetic model and optimal Vancomycin dosing regimen for...

This study aimed to develop and evaluate a population pharmacokinetic model and optimal dosing regimen for vancomycin in overweight and obese adults.

A population pharmacokinetic model using a two-compartment system was constructed using a nonlinear mixed-effects approach, incorporating 527 data points from 184 participants. External validation of the model was carried out using an additional 55 data points from 21 participants; these were not used in the construction of the model. Monte Carlo simulations were used to determine the dosage that achieved the steady state area under the curve value falling between 400 μg h/mL and 600 μg h/mL.

In the final model, vancomycin clearance was found to be a significant predictor of blood vancomycin levels, alongside creatinine clearance (CCr), blood urea nitrogen levels, and incidence of heart failure. CCr was calculated with adjusted body weight (AdjBW). AdjBW was selected as a predictor of the volume of distribution in the central and peripheral compartments. External validation showed that the highest proportion of cases had deviations of less than 15 % between measured and predicted values in the final model developed in this study. This indicates that our model outperforms previously developed models (five for obese patients and four for non-obese patients).

Our model shows that determining effective vancomycin doses for overweight and obese patients depend on estimated CCr rates, AdjBW, BUN levels, and incidence of heart failure.