Impact of Various Estimated Glomerular Filtration Rate Equations on the Pharmacokinetics of Meropenem in Critically Ill Adults
Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine..
IMPORTANCE: Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill.
OBJECTIVES: This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance.
DESIGN SETTING AND PARTICIPANTS: This single-center study evaluated adults hospitalized in an ICU who received IV meropenem from 2018 to 2022. Patients were excluded if they had acute kidney injury, were on kidney replacement therapy, or were treated with extracorporeal membrane oxygenation. Two cohorts were used for population pharmacokinetic modeling: a richly sampled development cohort (n = 19) and an opportunistically sampled qualification cohort (n = 32).
MAIN OUTCOMES AND MEASURES: A nonlinear mixed-effects model was developed using parametric methods to estimate meropenem serum concentrations.
RESULTS: The best-fit structural model in the richly sampled development cohort was a two-compartment model with first-order elimination. The final model included time-dependent weight normalized to a 70-kg adult as a covariate for volume of distribution (Vd) and time-dependent eGFR for clearance. Among the eGFR equations evaluated, eGFR based on creatinine and cystatin C expressed in mL/min best-predicted meropenem clearance. The mean (se) Vd in the final model was 18.2 (3.5) liters and clearance was 11.5 (1.3) L/hr. Using the development cohort as the Bayesian prior, the opportunistically sampled cohort demonstrated good accuracy and low bias.
CONCLUSIONS AND RELEVANCE: Contemporary eGFR equations that use both creatinine and cystatin C improved meropenem population pharmacokinetic model performance compared with creatinine-only or cystatin C-only eGFR equations in adult critically ill patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
Critical care explorations - 5(2023), 12 vom: 08. Dez., Seite e1011 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Barreto, Erin F [VerfasserIn] |
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| Links: |
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| Themen: |
Beta-lactams |
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| Anmerkungen: |
Date Revised 10.02.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1097/CCE.0000000000001011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Barreto, Erin F |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Impact of Various Estimated Glomerular Filtration Rate Equations on the Pharmacokinetics of Meropenem in Critically Ill Adults |
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| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine. | ||
| 520 | |a IMPORTANCE: Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill | ||
| 520 | |a OBJECTIVES: This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance | ||
| 520 | |a DESIGN SETTING AND PARTICIPANTS: This single-center study evaluated adults hospitalized in an ICU who received IV meropenem from 2018 to 2022. Patients were excluded if they had acute kidney injury, were on kidney replacement therapy, or were treated with extracorporeal membrane oxygenation. Two cohorts were used for population pharmacokinetic modeling: a richly sampled development cohort (n = 19) and an opportunistically sampled qualification cohort (n = 32) | ||
| 520 | |a MAIN OUTCOMES AND MEASURES: A nonlinear mixed-effects model was developed using parametric methods to estimate meropenem serum concentrations | ||
| 520 | |a RESULTS: The best-fit structural model in the richly sampled development cohort was a two-compartment model with first-order elimination. The final model included time-dependent weight normalized to a 70-kg adult as a covariate for volume of distribution (Vd) and time-dependent eGFR for clearance. Among the eGFR equations evaluated, eGFR based on creatinine and cystatin C expressed in mL/min best-predicted meropenem clearance. The mean (se) Vd in the final model was 18.2 (3.5) liters and clearance was 11.5 (1.3) L/hr. Using the development cohort as the Bayesian prior, the opportunistically sampled cohort demonstrated good accuracy and low bias | ||
| 520 | |a CONCLUSIONS AND RELEVANCE: Contemporary eGFR equations that use both creatinine and cystatin C improved meropenem population pharmacokinetic model performance compared with creatinine-only or cystatin C-only eGFR equations in adult critically ill patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a beta-lactams | |
| 650 | 4 | |a critical illness | |
| 650 | 4 | |a cystatin C | |
| 650 | 4 | |a extended-spectrum beta-lactamase | |
| 650 | 4 | |a multidrug resistance | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a sepsis | |
| 700 | 1 | |a Chang, Jack |e verfasserin |4 aut | |
| 700 | 1 | |a Rule, Andrew D |e verfasserin |4 aut | |
| 700 | 1 | |a Mara, Kristin C |e verfasserin |4 aut | |
| 700 | 1 | |a Meade, Laurie A |e verfasserin |4 aut | |
| 700 | 1 | |a Paul, Johar |e verfasserin |4 aut | |
| 700 | 1 | |a Jannetto, Paul J |e verfasserin |4 aut | |
| 700 | 1 | |a Athreya, Arjun P |e verfasserin |4 aut | |
| 700 | 1 | |a Scheetz, Marc H |e verfasserin |4 aut | |
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