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 m2 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): V1i = V1pop × (BW/70)1, Qi = Qpop × (BW/70)0.75, V2i = V2pop × (BW/70)1, CLi = (CLpop × (BW/70)0.75) × (eGFR/100)0.378) for patients without CRRT and CLi = (CLpop × (BW/70)0.75) × 0.9 for patients with CRRT, where CLpop, V1pop, Qpop, and V2pop 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
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| Enthalten in: |
European journal of clinical pharmacology - 76(2020), 1 vom: 25. Jan., Seite 61-71 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rapp, Mélanie [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Bacterial Agents |
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| Anmerkungen: |
Date Completed 28.09.2020 Date Revised 28.09.2020 published: Print-Electronic Citation Status MEDLINE |
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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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| PPN (Katalog-ID): |
NLM302589295 |
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| 100 | 1 | |a Rapp, Mélanie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Population pharmacokinetics of meropenem in critically ill children with different renal functions |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 28.09.2020 | ||
| 500 | |a Date Revised 28.09.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 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 | ||
| 520 | |a METHODS: Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem PK was investigated using a non-linear mixed-effect modeling approach | ||
| 520 | |a 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 m2 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): V1i = V1pop × (BW/70)1, Qi = Qpop × (BW/70)0.75, V2i = V2pop × (BW/70)1, CLi = (CLpop × (BW/70)0.75) × (eGFR/100)0.378) for patients without CRRT and CLi = (CLpop × (BW/70)0.75) × 0.9 for patients with CRRT, where CLpop, V1pop, Qpop, and V2pop 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 | ||
| 520 | |a CONCLUSION: Continuous infusion allows reaching the fT > MIC targets safely in children with normal or increased renal clearance | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Critically ill children | |
| 650 | 4 | |a Meropenem | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Meropenem |2 NLM | |
| 650 | 7 | |a FV9J3JU8B1 |2 NLM | |
| 700 | 1 | |a Urien, Saïk |e verfasserin |4 aut | |
| 700 | 1 | |a Foissac, Frantz |e verfasserin |4 aut | |
| 700 | 1 | |a Béranger, Agathe |e verfasserin |4 aut | |
| 700 | 1 | |a Bouazza, Naïm |e verfasserin |4 aut | |
| 700 | 1 | |a Benaboud, Sihem |e verfasserin |4 aut | |
| 700 | 1 | |a Bille, Emmanuelle |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Gana, Inès |e verfasserin |4 aut | |
| 700 | 1 | |a Moulin, Florence |e verfasserin |4 aut | |
| 700 | 1 | |a Lesage, Fabrice |e verfasserin |4 aut | |
| 700 | 1 | |a Renolleau, Sylvain |e verfasserin |4 aut | |
| 700 | 1 | |a Tréluyer, Jean Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Hirt, Déborah |e verfasserin |4 aut | |
| 700 | 1 | |a Oualha, Mehdi |e verfasserin |4 aut | |
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