Vancomycin loading dose individualization in a population of obese patients undergoing haemodialysis based on population pharmacokinetic model

Abstract

This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment. Therapeutic drug monitoring data from 27 patients with a BMI of 30.2–52.9 kg/m² were analysed. Among all tested variables, only LBM as a covariate of vancomycin Vd significantly improved the model, while vancomycin CL did not correlate with any of the tested variables. The median (IQR) value from the conditional mean of individual estimates of Vd and CL was 68.4 (56.6–84.2) L and 0.86 (0.79–0.90) L/h, respectively. To ensure optimal vancomycin exposure during the first 48 h of therapy, the vancomycin loading dose of 1500, 1750, 2000, 2250, 2500 and 2750 mg should be administered to obese patients with a lean body mass of ˂50, 50–60, 60–70, 70–80, 80–85 and >85 kg, respectively.

Keywords:

• Chronic kidney disease
• acute kidney injury
• lean body mass
• Monte Carlo simulation
• nonlinear mixed-effects modelling
• therapeutic drug monitoring

Acknowledgments

We are very grateful to the physicians, nurses and other clinical pharmacists of General University Hospital in Prague and Military University Hospital Prague for their cooperation in careful collecting samples for this study.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics approval statement

The study was approved by the Ethics Committee of Military University Hospital in Prague under the registration number 108/17-42/2022 on April 25, 2022, and followed the principles of the Declaration of Helsinki.

Disclosure statement

The authors have no conflicts of interest to declare.

Additional information

Funding

This study was supported by Ministry of Health of Czech Republic project MH CZ-DRO-VFN64165 and by the Charles University project Cooperatio (research area PHAR).