Meropenem Model-Informed Precision Dosing in the Treatment of Critically Ill Patients: Can We Use It?
The number of pharmacokinetic (PK) models of meropenem is increasing. However, the daily role of these PK models in the clinic remains unclear, especially for critically ill patients. Therefore, we evaluated the published meropenem models on real-world ICU data to assess their suitability for use in...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/12/2/383 |
| _version_ | 1797622787068657664 |
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| author | Letao Li Sebastiaan D. T. Sassen Tim M. J. Ewoldt Alan Abdulla Nicole G. M. Hunfeld Anouk E. Muller Brenda C. M. de Winter Henrik Endeman Birgit C. P. Koch |
| author_facet | Letao Li Sebastiaan D. T. Sassen Tim M. J. Ewoldt Alan Abdulla Nicole G. M. Hunfeld Anouk E. Muller Brenda C. M. de Winter Henrik Endeman Birgit C. P. Koch |
| author_sort | Letao Li |
| collection | DOAJ |
| description | The number of pharmacokinetic (PK) models of meropenem is increasing. However, the daily role of these PK models in the clinic remains unclear, especially for critically ill patients. Therefore, we evaluated the published meropenem models on real-world ICU data to assess their suitability for use in clinical practice. All models were built in NONMEM and evaluated using prediction and simulation-based diagnostics for the ability to predict the subsequent meropenem concentrations without plasma concentrations (a priori), and with plasma concentrations (a posteriori), for use in therapeutic drug monitoring (TDM). Eighteen PopPK models were included for evaluation. The a priori fit of the models, without the use of plasma concentrations, was poor, with a prediction error (PE)% of the interquartile range (IQR) exceeding the ±30% threshold. The fit improved when one to three concentrations were used to improve model predictions for TDM purposes. Two models were in the acceptable range with an IQR PE% within ±30%, when two or three concentrations were used. The role of PK models to determine the starting dose of meropenem in this population seems limited. However, certain models might be suitable for TDM-based dose adjustment using two to three plasma concentrations. |
| first_indexed | 2024-03-11T09:15:14Z |
| format | Article |
| id | doaj.art-aa2133f593ba423898dabeb780442696 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-11T09:15:14Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-aa2133f593ba423898dabeb7804426962023-11-16T18:44:16ZengMDPI AGAntibiotics2079-63822023-02-0112238310.3390/antibiotics12020383Meropenem Model-Informed Precision Dosing in the Treatment of Critically Ill Patients: Can We Use It?Letao Li0Sebastiaan D. T. Sassen1Tim M. J. Ewoldt2Alan Abdulla3Nicole G. M. Hunfeld4Anouk E. Muller5Brenda C. M. de Winter6Henrik Endeman7Birgit C. P. Koch8Department of Hospital Pharmacy, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Hospital Pharmacy, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Hospital Pharmacy, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Hospital Pharmacy, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Hospital Pharmacy, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsCenter for Antimicrobial Treatment Optimization Rotterdam (CATOR), 3015 GD Rotterdam, The NetherlandsDepartment of Hospital Pharmacy, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Intensive Care, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Hospital Pharmacy, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsThe number of pharmacokinetic (PK) models of meropenem is increasing. However, the daily role of these PK models in the clinic remains unclear, especially for critically ill patients. Therefore, we evaluated the published meropenem models on real-world ICU data to assess their suitability for use in clinical practice. All models were built in NONMEM and evaluated using prediction and simulation-based diagnostics for the ability to predict the subsequent meropenem concentrations without plasma concentrations (a priori), and with plasma concentrations (a posteriori), for use in therapeutic drug monitoring (TDM). Eighteen PopPK models were included for evaluation. The a priori fit of the models, without the use of plasma concentrations, was poor, with a prediction error (PE)% of the interquartile range (IQR) exceeding the ±30% threshold. The fit improved when one to three concentrations were used to improve model predictions for TDM purposes. Two models were in the acceptable range with an IQR PE% within ±30%, when two or three concentrations were used. The role of PK models to determine the starting dose of meropenem in this population seems limited. However, certain models might be suitable for TDM-based dose adjustment using two to three plasma concentrations.https://www.mdpi.com/2079-6382/12/2/383meropenemICUpopulation pharmacokineticsmodel validationreal-world patientsmodel-informed precision dosing |
| spellingShingle | Letao Li Sebastiaan D. T. Sassen Tim M. J. Ewoldt Alan Abdulla Nicole G. M. Hunfeld Anouk E. Muller Brenda C. M. de Winter Henrik Endeman Birgit C. P. Koch Meropenem Model-Informed Precision Dosing in the Treatment of Critically Ill Patients: Can We Use It? Antibiotics meropenem ICU population pharmacokinetics model validation real-world patients model-informed precision dosing |
| title | Meropenem Model-Informed Precision Dosing in the Treatment of Critically Ill Patients: Can We Use It? |
| title_full | Meropenem Model-Informed Precision Dosing in the Treatment of Critically Ill Patients: Can We Use It? |
| title_fullStr | Meropenem Model-Informed Precision Dosing in the Treatment of Critically Ill Patients: Can We Use It? |
| title_full_unstemmed | Meropenem Model-Informed Precision Dosing in the Treatment of Critically Ill Patients: Can We Use It? |
| title_short | Meropenem Model-Informed Precision Dosing in the Treatment of Critically Ill Patients: Can We Use It? |
| title_sort | meropenem model informed precision dosing in the treatment of critically ill patients can we use it |
| topic | meropenem ICU population pharmacokinetics model validation real-world patients model-informed precision dosing |
| url | https://www.mdpi.com/2079-6382/12/2/383 |
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