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Published on: March 3, 2023
Pharmacokinetics of Vancomycin in Elderly Patients Aged over 80 Years
Laurent Bourguignon1, Yoann Cazaubon2, Guillaume Debeurme3
1Hospices Civils de Lyon, Groupement Hospitalier de Gériatrie, Hôpital Antoine Charial, Service Pharmaceutique, Francheville, France UMR CNRS 5558, Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, Lyon, France ISPB, Faculté de Pharmacie, Université Lyon 1, Lyon, France laurent.bourguignon@chu-lyon.fr.
Abstract:
Since the 1950s, vancomycin has remained a reference treatment for severe infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus Vancomycin is a nephrotoxic and ototoxic drug mainly eliminated through the kidneys. It has a large interindividual pharmacokinetic variability, which justifies monitoring its plasma concentrations in patients. This is especially important in patients aged over 80 years, who frequently have renal impairment. However, the pharmacokinetics of vancomycin in this population is very poorly described in the literature. The objective of this work was to propose a model able to predict the pharmacokinetics of vancomycin in very elderly people. First, a population pharmacokinetic model was carried out using the algorithm NPAG (nonparametric adaptive grid) on a database of 70 hospitalized patients aged over 80 years and treated with vancomycin. An external validation then was performed on 41 patients, and the predictive capabilities of the model were assessed. The model had two compartments and six parameters. Body weight and creatinine clearance significantly influenced vancomycin volume of distribution and body clearance, respectively. The means (± standard deviations) of vancomycin volume of distribution and clearance were 36.3 ± 15.2 liter and 2.0 ± 0.9 liter/h, respectively. In the validation group, the bias and precision were -0.75 mg/liter and 8.76 mg/liter for population predictions and -0.39 mg/liter and 2.68 mg/liter for individual predictions. In conclusion, a pharmacokinetic model of vancomycin in a very elderly population has been created and validated for predicting plasma concentrations of vancomycin.
Insights
A new pharmacokinetic model predicts vancomycin levels in elderly patients over 80. This model accounts for body weight and renal function, improving vancomycin dosing for this vulnerable population.
Area of Science:
- Pharmacology
- Geriatric Medicine
- Clinical Pharmacy
Background:
- Vancomycin is a critical antibiotic for Gram-positive infections, including MRSA.
- It exhibits significant pharmacokinetic variability and is nephrotoxic/ototoxic, requiring therapeutic drug monitoring.
- Elderly patients (>80 years) often have renal impairment, complicating vancomycin dosing.
Purpose of the Study:
- To develop and validate a population pharmacokinetic model for vancomycin in patients over 80 years old.
- To improve the prediction of vancomycin plasma concentrations in this specific demographic.
- To aid in optimizing vancomycin therapy for very elderly individuals.
Main Methods:
- A population pharmacokinetic model was developed using the Nonparametric Adaptive Grid (NPAG) algorithm.
- Data from 70 hospitalized patients over 80 treated with vancomycin were used for model building.
- External validation was performed on a separate group of 41 patients.
Main Results:
- The final model comprised two compartments and six parameters.
- Body weight and creatinine clearance were significant predictors of vancomycin volume of distribution and body clearance, respectively.
- The model demonstrated good predictive capabilities with low bias and high precision in the validation group.
Conclusions:
- A validated pharmacokinetic model for vancomycin in very elderly patients has been established.
- This model can accurately predict vancomycin plasma concentrations in individuals over 80.
- The findings support improved vancomycin dosing strategies for the geriatric population.
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