Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblance
Abstract Vancomycin is an antibiotic used for severe infections. To ensure microbiological efficacy, a ratio of AUC/MIC ≥400 is recommended. However, there is significant interindividual variability in its pharmacokinetic parameters, necessitating therapeutic drug monitoring to adjust dosing regimen...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.13253 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841555917654458368 |
|---|---|
| author | Peggy Gandia Sahira Chaiben Nicolas Fabre Didier Concordet |
| author_facet | Peggy Gandia Sahira Chaiben Nicolas Fabre Didier Concordet |
| author_sort | Peggy Gandia |
| collection | DOAJ |
| description | Abstract Vancomycin is an antibiotic used for severe infections. To ensure microbiological efficacy, a ratio of AUC/MIC ≥400 is recommended. However, there is significant interindividual variability in its pharmacokinetic parameters, necessitating therapeutic drug monitoring to adjust dosing regimens and ensure efficacy while avoiding toxicity. Population pharmacokinetic (PopPK) models enable dose personalization, but the challenge lies in the choice of the model to use among the multitude of models in the literature. We compared 18 PopPK models created from populations with the same sociodemographic and clinicobiological characteristics. Simulations were performed for a 47 years old man, weighing 70 kg, with an albumin level of 35.5 g/L, a creatinine clearance of 100 mL/min, an eGFR of 106 mL/min/1.73 m2, and receiving an intravenous infusion of 1 g × 2/day of VCM over 1 h for 48 h. Simulations of time–concentration profiles revealed differences, leading us to determine the probability of achieving microbiological efficacy (AUC/MIC ≥ 400) with each model. Depending on some models, a dose of 1 g × 2/day is required to ensure microbiological efficacy in over 90% of the population, while with the same dose other models do not exceed 10% of the population. To ensure that 90% of the patients are correctly exposed, a dose of vancomycin ranging from 0.9 g × 2/day to 2.2 g × 2/day is necessary a priori depending on the chosen model. These differences raise an issue in choosing a model for performing therapeutic drug monitoring using a PopPK model with or without Bayesian approach. Thus, it is fundamental to evaluate the impact of these differences on both efficacy/toxicity. |
| format | Article |
| id | doaj-art-a85f0cd7f4c84c07a3d8cc94846a9a34 |
| institution | Kabale University |
| issn | 2163-8306 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj-art-a85f0cd7f4c84c07a3d8cc94846a9a342025-01-07T20:48:59ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062025-01-0114114215110.1002/psp4.13253Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblancePeggy Gandia0Sahira Chaiben1Nicolas Fabre2Didier Concordet3Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology Toulouse University Hospital Toulouse FranceINTHERES Université de Toulouse, INRAE, ENVT Toulouse FranceUMR 152 PharmaDev University of Toulouse, IRD, UPS Toulouse FranceINTHERES Université de Toulouse, INRAE, ENVT Toulouse FranceAbstract Vancomycin is an antibiotic used for severe infections. To ensure microbiological efficacy, a ratio of AUC/MIC ≥400 is recommended. However, there is significant interindividual variability in its pharmacokinetic parameters, necessitating therapeutic drug monitoring to adjust dosing regimens and ensure efficacy while avoiding toxicity. Population pharmacokinetic (PopPK) models enable dose personalization, but the challenge lies in the choice of the model to use among the multitude of models in the literature. We compared 18 PopPK models created from populations with the same sociodemographic and clinicobiological characteristics. Simulations were performed for a 47 years old man, weighing 70 kg, with an albumin level of 35.5 g/L, a creatinine clearance of 100 mL/min, an eGFR of 106 mL/min/1.73 m2, and receiving an intravenous infusion of 1 g × 2/day of VCM over 1 h for 48 h. Simulations of time–concentration profiles revealed differences, leading us to determine the probability of achieving microbiological efficacy (AUC/MIC ≥ 400) with each model. Depending on some models, a dose of 1 g × 2/day is required to ensure microbiological efficacy in over 90% of the population, while with the same dose other models do not exceed 10% of the population. To ensure that 90% of the patients are correctly exposed, a dose of vancomycin ranging from 0.9 g × 2/day to 2.2 g × 2/day is necessary a priori depending on the chosen model. These differences raise an issue in choosing a model for performing therapeutic drug monitoring using a PopPK model with or without Bayesian approach. Thus, it is fundamental to evaluate the impact of these differences on both efficacy/toxicity.https://doi.org/10.1002/psp4.13253 |
| spellingShingle | Peggy Gandia Sahira Chaiben Nicolas Fabre Didier Concordet Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblance CPT: Pharmacometrics & Systems Pharmacology |
| title | Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblance |
| title_full | Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblance |
| title_fullStr | Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblance |
| title_full_unstemmed | Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblance |
| title_short | Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblance |
| title_sort | vancomycin population pharmacokinetic models uncovering pharmacodynamic divergence amid clinicobiological resemblance |
| url | https://doi.org/10.1002/psp4.13253 |
| work_keys_str_mv | AT peggygandia vancomycinpopulationpharmacokineticmodelsuncoveringpharmacodynamicdivergenceamidclinicobiologicalresemblance AT sahirachaiben vancomycinpopulationpharmacokineticmodelsuncoveringpharmacodynamicdivergenceamidclinicobiologicalresemblance AT nicolasfabre vancomycinpopulationpharmacokineticmodelsuncoveringpharmacodynamicdivergenceamidclinicobiologicalresemblance AT didierconcordet vancomycinpopulationpharmacokineticmodelsuncoveringpharmacodynamicdivergenceamidclinicobiologicalresemblance |