Model Re-Estimation: An Alternative for Poor Predictive Performance during External Evaluations? Example of Gentamicin in Critically Ill Patients.
dosing nomogram
external evaluation
gentamicin
model re-estimation
population pharmacokinetic modeling
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
07 Jul 2022
07 Jul 2022
Historique:
received:
22
04
2022
revised:
03
06
2022
accepted:
06
07
2022
entrez:
27
7
2022
pubmed:
28
7
2022
medline:
28
7
2022
Statut:
epublish
Résumé
An external evaluation is crucial before clinical applications; however, only a few gentamicin population pharmacokinetic (PopPK) models for critically ill patients included it in the model development. In this study, we aimed to evaluate gentamicin PopPK models developed for critically ill patients. The evaluated models were selected following a literature review on aminoglycoside PopPK models for critically ill patients. The data of patients were retrospectively collected from two Quebec hospitals, the external evaluation and model re-estimation were performed with NONMEM From the datasets of 39 and 48 patients from the two Quebec hospitals, none of the evaluated models presented acceptable values for bias and imprecision. Following model re-estimations, all models showed an acceptable predictive performance. An a priori dosing nomogram was developed with the best performing re-estimated model and was consistent based on recommended dosing regimens. Due to the poor predictive performance during the external evaluations, the latter must be prioritized during model development. Model re-estimation may be an alternative to developing a new model, especially when most known models display similar covariates.
Sections du résumé
BACKGROUND
BACKGROUND
An external evaluation is crucial before clinical applications; however, only a few gentamicin population pharmacokinetic (PopPK) models for critically ill patients included it in the model development. In this study, we aimed to evaluate gentamicin PopPK models developed for critically ill patients.
METHODS
METHODS
The evaluated models were selected following a literature review on aminoglycoside PopPK models for critically ill patients. The data of patients were retrospectively collected from two Quebec hospitals, the external evaluation and model re-estimation were performed with NONMEM
RESULTS
RESULTS
From the datasets of 39 and 48 patients from the two Quebec hospitals, none of the evaluated models presented acceptable values for bias and imprecision. Following model re-estimations, all models showed an acceptable predictive performance. An a priori dosing nomogram was developed with the best performing re-estimated model and was consistent based on recommended dosing regimens.
CONCLUSION
CONCLUSIONS
Due to the poor predictive performance during the external evaluations, the latter must be prioritized during model development. Model re-estimation may be an alternative to developing a new model, especially when most known models display similar covariates.
Identifiants
pubmed: 35890322
pii: pharmaceutics14071426
doi: 10.3390/pharmaceutics14071426
pmc: PMC9315759
pii:
doi:
Types de publication
Journal Article
Langues
eng
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