Greppmair, Sebastian and Brinkmann, Alexander and Roehr, Anka and Frey, Otto and Hagel, Stefan and Dorn, Christoph and Marsot, Amelie and El-Haffaf, Ibrahim and Zoller, Michael and Saller, Thomas and Zander, Johannes and Schatz, Lea Marie and Scharf, Christina and Briegel, Josef and Minichmayr, Iris K. and Wicha, Sebastian G. and Liebchen, Uwe (2023) Towards model-informed precision dosing of piperacillin: multicenter systematic external evaluation of pharmacokinetic models in critically ill adults with a focus on Bayesian forecasting. INTENSIVE CARE MEDICINE, 49 (8). pp. 966-976. ISSN 0342-4642, 1432-1238
Full text not available from this repository. (Request a copy)Abstract
PurposeInadequate piperacillin (PIP) exposure in intensive care unit (ICU) patients threatens therapeutic success. Model-informed precision dosing (MIPD) might be promising to individualize dosing; however, the transferability of published models to external populations is uncertain. This study aimed to externally evaluate the available PIP population pharmacokinetic (PopPK) models.MethodsA multicenter dataset of 561 ICU patients (11 centers/3654 concentrations) was used for the evaluation of 24 identified models. Model performance was investigated for a priori (A) predictions, i.e., considering dosing records and patient characteristics only, and for Bayesian forecasting, i.e., additionally including the first (B1) or first and second (B2) therapeutic drug monitoring (TDM) samples per patient. Median relative prediction error (MPE) [%] and median absolute relative prediction error (MAPE) [%] were calculated to quantify accuracy and precision.ResultsThe evaluation revealed a large inter-model variability (A: MPE - 135.6-78.3% and MAPE 35.7-135.6%). Integration of TDM data improved all model predictions (B1/B2 relative improvement vs. A: |MPE|(median_all_models) 45.1/67.5%; MAPE(median_all_models) 29/39%). The model by Kim et al. was identified to be most appropriate for the total dataset (A/B1/B2: MPE - 9.8/- 5.9/- 0.9%; MAPE 37/27.3/23.7%), Udy et al. performed best in patients receiving intermittent infusion, and Klastrup et al. best predicted patients receiving continuous infusion. Additional evaluations stratified by sex and renal replacement therapy revealed further promising models.ConclusionThe predictive performance of published PIP models in ICU patients varied considerably, highlighting the relevance of appropriate model selection for MIPD. Our differentiated external evaluation identified specific models suitable for clinical use, especially in combination with TDM.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BETA-LACTAM ANTIBIOTICS; CARE; HEMODIAFILTRATION; DETERMINANT; PREDICTION; SUFFICIENT; THERAPY; SEPSIS; Intensive care medicine; Model-informed precision dosing; Piperacillin; Pharmacokinetics; pharmacodynamics; Therapeutic drug monitoring |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2024 06:10 |
| Last Modified: | 09 Apr 2024 06:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60672 |
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