Piperacillin Population Pharmacokinetics and Dosing Regimen Optimization in Critically Ill Children with Normal and Augmented Renal Clearance
BACKGROUND: Critically ill children frequently display observed alterations of pharmacokinetic (PK) parameters, leading to a reduction in β-lactam concentrations. This study aimed to develop a PK population model for piperacillin in order to optimize individual dosing regimens.
METHODS: All children aged ≤ 18 years, weighing more than 2.5 kg, and receiving piperacillin infusions were included in this study. Piperacillin was quantified by high-performance liquid chromatography, and PK were described using the non-linear mixed-effect modeling software MONOLIX. Monte Carlo simulations were used to optimize dosing regimens in order to attain two PK targets: 50% fT>MIC and 100% fT>MIC.
RESULTS: We included 50 children with a median (range) postnatal age of 2.3 years (0.1-18), body weight (BW) of 11.9 kg (2.7-50), Pediatric Logistic Organ Dysfunction-2 (PELOD-2) severity score of 4 (0-16), and estimated glomerular filtration rate (eGFR) of 142 mL.min-1.1.73 m-2 (29-675). A one-compartment model with first-order elimination adequately described the data. Median (range) values for piperacillin clearance (CL) and volume of distribution were 3 L.h-1 (0.71-10) and 0.33 L.kg-1 (0.21-0.86), respectively. BW was integrated with the allometric relationship. eGFR and PELOD-2 severity score were the covariates explaining between-subject variability in CL and volume, respectively. According to the simulations, extended and continuous infusion provided the highest probability of reaching the target of 50% fT>MIC and 100% fT>MIC for normal and augmented renal clearance, respectively.
CONCLUSIONS: Unlike standard intermittent piperacillin dosing regimens, extended and continuous infusion allows the PK targets to be reached, for children with normal or augmented renal clearance.
TRIAL REGISTRATION NUMBER: Registered at http://www.clinicaltrials.gov (NCT02539407).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:58 |
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| Enthalten in: |
Clinical pharmacokinetics - 58(2019), 2 vom: 04. Feb., Seite 223-233 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Béranger, Agathe [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Bacterial Agents |
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| Anmerkungen: |
Date Completed 09.04.2020 Date Revised 09.04.2020 published: Print ClinicalTrials.gov: NCT02539407 Citation Status MEDLINE |
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| doi: |
10.1007/s40262-018-0682-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM285076051 |
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| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT02539407 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Critically ill children frequently display observed alterations of pharmacokinetic (PK) parameters, leading to a reduction in β-lactam concentrations. This study aimed to develop a PK population model for piperacillin in order to optimize individual dosing regimens | ||
| 520 | |a METHODS: All children aged ≤ 18 years, weighing more than 2.5 kg, and receiving piperacillin infusions were included in this study. Piperacillin was quantified by high-performance liquid chromatography, and PK were described using the non-linear mixed-effect modeling software MONOLIX. Monte Carlo simulations were used to optimize dosing regimens in order to attain two PK targets: 50% fT>MIC and 100% fT>MIC | ||
| 520 | |a RESULTS: We included 50 children with a median (range) postnatal age of 2.3 years (0.1-18), body weight (BW) of 11.9 kg (2.7-50), Pediatric Logistic Organ Dysfunction-2 (PELOD-2) severity score of 4 (0-16), and estimated glomerular filtration rate (eGFR) of 142 mL.min-1.1.73 m-2 (29-675). A one-compartment model with first-order elimination adequately described the data. Median (range) values for piperacillin clearance (CL) and volume of distribution were 3 L.h-1 (0.71-10) and 0.33 L.kg-1 (0.21-0.86), respectively. BW was integrated with the allometric relationship. eGFR and PELOD-2 severity score were the covariates explaining between-subject variability in CL and volume, respectively. According to the simulations, extended and continuous infusion provided the highest probability of reaching the target of 50% fT>MIC and 100% fT>MIC for normal and augmented renal clearance, respectively | ||
| 520 | |a CONCLUSIONS: Unlike standard intermittent piperacillin dosing regimens, extended and continuous infusion allows the PK targets to be reached, for children with normal or augmented renal clearance | ||
| 520 | |a TRIAL REGISTRATION NUMBER: Registered at http://www.clinicaltrials.gov (NCT02539407) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Tazobactam |2 NLM | |
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| 700 | 1 | |a Urien, Saïk |e verfasserin |4 aut | |
| 700 | 1 | |a Moulin, Florence |e verfasserin |4 aut | |
| 700 | 1 | |a Bille, Emmanuelle |e verfasserin |4 aut | |
| 700 | 1 | |a Lesage, Fabrice |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Genuini, Mathieu |e verfasserin |4 aut | |
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| 700 | 1 | |a Tréluyer, Jean-Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Oualha, Mehdi |e verfasserin |4 aut | |
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