Vancomycin loading dose individualization in a population of obese patients undergoing haemodialysis based on population pharmacokinetic model
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
- Keywords
- Chronic kidney disease, Monte Carlo simulation, acute kidney injury, lean body mass, nonlinear mixed-effects modelling, therapeutic drug monitoring,
- MeSH
- Anti-Bacterial Agents * pharmacokinetics administration & dosage MeSH
- Models, Biological MeSH
- Renal Dialysis * methods MeSH
- Adult MeSH
- Body Mass Index MeSH
- Middle Aged MeSH
- Humans MeSH
- Monte Carlo Method MeSH
- Drug Monitoring methods MeSH
- Obesity * complications metabolism MeSH
- Area Under Curve MeSH
- Cross-Sectional Studies MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Vancomycin * pharmacokinetics administration & dosage MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Bacterial Agents * MeSH
- Vancomycin * MeSH
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.
Department of Applied Pharmacy Faculty of Pharmacy Masaryk University Brno Czech Republic
Department of Clinical Pharmacy Military University Hospital Prague Prague Czech Republic
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