Population pharmacokinetics of meropenem in critically ill children with different renal functions
Purpose We aimed to develop a meropenem population pharmacokinetic (PK) model in critically ill children and simulate dosing regimens in order to optimize patient exposure. Methods Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem PK was investigated using a non-linear mixed-effect modeling approach. Results Forty patients with an age of 16.8 (1.4–187.2) months, weight of 9.1 (3.8–59) kg, and estimated glomerular filtration rate (eGFR) of 151 (19–440) mL/min/1.73 $ m^{2} $ were included. Eleven patients received continuous replacement renal therapy (CRRT). Concentration-time courses were best described by a two-compartment model with first-order elimination. Body weight (BW), eGFR, and CRRT were covariates explaining the between-subject variabilities on central/peripheral volume of distribution (V1/V2), inter-compartment clearance (Q), and clearance (CL): $ V1_{i} $ = $ V1_{pop} $ × (BW/70)1, Qi = Qpop × (BW/70)0.75, $ V2_{i} $ = $ V2_{pop} $ × (BW/70)1, $ CL_{i} $ = ($ CL_{pop} $ × (BW/70)0.75) × (eGFR/100)0.378) for patients without CRRT and $ CL_{i} $ = ($ CL_{pop} $ × (BW/70)0.75) × 0.9 for patients with CRRT, where $ CL_{pop} $, $ V1_{pop} $, Qpop, and $ V2_{pop} $ are 6.82 L/h, 40.6 L, 1 L/h, and 9.2 L respectively normalized to a 70-kg subject. Continuous infusion, 60 and 120 mg/kg per day, is the most adequate dosing regimen to attain the target of 50% fT > MIC and 100% fT > MIC for patients infected by bacteria with high minimum inhibitory concentration (MIC) value (> 4 mg/L) without risk of accumulation except in children with severe renal failure. Conclusion Continuous infusion allows reaching the fT > MIC targets safely in children with normal or increased renal clearance..
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Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
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| Enthalten in: |
European journal of clinical pharmacology - 76(2019), 1 vom: 26. Okt., Seite 61-71 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rapp, Mélanie [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
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| Anmerkungen: |
© Springer-Verlag GmbH Germany, part of Springer Nature 2019 |
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| doi: |
10.1007/s00228-019-02761-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Purpose We aimed to develop a meropenem population pharmacokinetic (PK) model in critically ill children and simulate dosing regimens in order to optimize patient exposure. Methods Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem PK was investigated using a non-linear mixed-effect modeling approach. Results Forty patients with an age of 16.8 (1.4–187.2) months, weight of 9.1 (3.8–59) kg, and estimated glomerular filtration rate (eGFR) of 151 (19–440) mL/min/1.73 $ m^{2} $ were included. Eleven patients received continuous replacement renal therapy (CRRT). Concentration-time courses were best described by a two-compartment model with first-order elimination. Body weight (BW), eGFR, and CRRT were covariates explaining the between-subject variabilities on central/peripheral volume of distribution (V1/V2), inter-compartment clearance (Q), and clearance (CL): $ V1_{i} $ = $ V1_{pop} $ × (BW/70)1, Qi = Qpop × (BW/70)0.75, $ V2_{i} $ = $ V2_{pop} $ × (BW/70)1, $ CL_{i} $ = ($ CL_{pop} $ × (BW/70)0.75) × (eGFR/100)0.378) for patients without CRRT and $ CL_{i} $ = ($ CL_{pop} $ × (BW/70)0.75) × 0.9 for patients with CRRT, where $ CL_{pop} $, $ V1_{pop} $, Qpop, and $ V2_{pop} $ are 6.82 L/h, 40.6 L, 1 L/h, and 9.2 L respectively normalized to a 70-kg subject. Continuous infusion, 60 and 120 mg/kg per day, is the most adequate dosing regimen to attain the target of 50% fT > MIC and 100% fT > MIC for patients infected by bacteria with high minimum inhibitory concentration (MIC) value (> 4 mg/L) without risk of accumulation except in children with severe renal failure. Conclusion Continuous infusion allows reaching the fT > MIC targets safely in children with normal or increased renal clearance. | ||
| 650 | 4 | |a Meropenem | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 4 | |a Critically ill children | |
| 700 | 1 | |a Urien, Saïk |4 aut | |
| 700 | 1 | |a Foissac, Frantz |4 aut | |
| 700 | 1 | |a Béranger, Agathe |4 aut | |
| 700 | 1 | |a Bouazza, Naïm |4 aut | |
| 700 | 1 | |a Benaboud, Sihem |4 aut | |
| 700 | 1 | |a Bille, Emmanuelle |4 aut | |
| 700 | 1 | |a Zheng, Yi |4 aut | |
| 700 | 1 | |a Gana, Inès |4 aut | |
| 700 | 1 | |a Moulin, Florence |4 aut | |
| 700 | 1 | |a Lesage, Fabrice |4 aut | |
| 700 | 1 | |a Renolleau, Sylvain |4 aut | |
| 700 | 1 | |a Tréluyer, Jean Marc |4 aut | |
| 700 | 1 | |a Hirt, Déborah |4 aut | |
| 700 | 1 | |a Oualha, Mehdi |4 aut | |
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