Piperacillin Population Pharmacokinetics and Dosing Regimen Optimization in Critically Ill Children Receiving Continuous Renal Replacement Therapy
We aimed to develop a piperacillin population pharmacokinetic (PK) model in critically ill children receiving continuous renal replacement therapy (CRRT) and to optimize dosing regimens. The piperacillin plasma concentration was quantified by high-performance liquid chromatography. Piperacillin PK was investigated using a nonlinear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration according to the target of 100% interdose interval time in which concentration is one to four times above the MIC (100% fT > 1 to 4× MIC). A total of 32 children with a median (interquartile range [IQR]) postnatal age of 2 years (0 to 11), body weight (BW) of 15 kg (6 to 38), and receiving CRRT were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. BW and residual diuresis (Qu) explained some between-subject variabilities on volume of distribution (V), where [Formula: see text], and clearance (CL), where [Formula: see text], where CLpop and Vpop are 6.78 L/h and 55.0 L, respectively, normalized to a 70-kg subject and median residual diuresis of 0.06 mL/kg/h. Simulations with intermittent and continuous administrations for 4 typical patients with different rates of residual diuresis (0, 0.1, 0.25, and 0.5 mL/kg/h) showed that continuous infusions were appropriate to attain the PK target for patients with residual diuresis higher than 0.1 mL/kg/h according to BW and MIC, while for anuric patients, less frequent intermittent doses were mandatory to avoid accumulation. Optimal exposure to piperacillin in critically ill children on CRRT should be achieved by using continuous infusions with escalating doses for high-MIC bacteria, except for anuric patients who require less frequent intermittent doses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:66 |
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| Enthalten in: |
Antimicrobial agents and chemotherapy - 66(2022), 12 vom: 20. Dez., Seite e0113522 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Thy, Michael [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.12.2022 Date Revised 08.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1128/aac.01135-22 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We aimed to develop a piperacillin population pharmacokinetic (PK) model in critically ill children receiving continuous renal replacement therapy (CRRT) and to optimize dosing regimens. The piperacillin plasma concentration was quantified by high-performance liquid chromatography. Piperacillin PK was investigated using a nonlinear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration according to the target of 100% interdose interval time in which concentration is one to four times above the MIC (100% fT > 1 to 4× MIC). A total of 32 children with a median (interquartile range [IQR]) postnatal age of 2 years (0 to 11), body weight (BW) of 15 kg (6 to 38), and receiving CRRT were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. BW and residual diuresis (Qu) explained some between-subject variabilities on volume of distribution (V), where [Formula: see text], and clearance (CL), where [Formula: see text], where CLpop and Vpop are 6.78 L/h and 55.0 L, respectively, normalized to a 70-kg subject and median residual diuresis of 0.06 mL/kg/h. Simulations with intermittent and continuous administrations for 4 typical patients with different rates of residual diuresis (0, 0.1, 0.25, and 0.5 mL/kg/h) showed that continuous infusions were appropriate to attain the PK target for patients with residual diuresis higher than 0.1 mL/kg/h according to BW and MIC, while for anuric patients, less frequent intermittent doses were mandatory to avoid accumulation. Optimal exposure to piperacillin in critically ill children on CRRT should be achieved by using continuous infusions with escalating doses for high-MIC bacteria, except for anuric patients who require less frequent intermittent doses | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a children | |
| 650 | 4 | |a critical care | |
| 650 | 4 | |a intensive care | |
| 650 | 4 | |a pediatric drug therapy | |
| 650 | 4 | |a pediatric infectious disease | |
| 650 | 4 | |a pharmacology | |
| 650 | 4 | |a piperacillin | |
| 650 | 4 | |a population pharmacokinetics | |
| 650 | 4 | |a renal failure | |
| 650 | 4 | |a renal replacement therapy | |
| 650 | 7 | |a Piperacillin |2 NLM | |
| 650 | 7 | |a X00B0D5O0E |2 NLM | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Piperacillin, Tazobactam Drug Combination |2 NLM | |
| 650 | 7 | |a 157044-21-8 |2 NLM | |
| 700 | 1 | |a Urien, Saïk |e verfasserin |4 aut | |
| 700 | 1 | |a Foissac, Frantz |e verfasserin |4 aut | |
| 700 | 1 | |a Bouazza, Naïm |e verfasserin |4 aut | |
| 700 | 1 | |a Gana, Inès |e verfasserin |4 aut | |
| 700 | 1 | |a Bille, Emmanuelle |e verfasserin |4 aut | |
| 700 | 1 | |a Béranger, Agathe |e verfasserin |4 aut | |
| 700 | 1 | |a Toubiana, Julie |e verfasserin |4 aut | |
| 700 | 1 | |a Berthaud, Romain |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 Benaboud, Sihem |e verfasserin |4 aut | |
| 700 | 1 | |a Oualha, Mehdi |e verfasserin |4 aut | |
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