Impact of Various Estimated Glomerular Filtration Rate Equations on the Pharmacokinetics of Meropenem in Critically Ill Adults.

Autor:	Barreto EF; Department of Pharmacy, Mayo Clinic, Rochester, MN., Chang J; Department of Pharmacy Practice, Chicago College of Pharmacy, Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, IL.; Department of Pharmacy, Northwestern Medicine, Chicago, IL., Rule AD; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.; Division of Epidemiology, Mayo Clinic, Rochester, MN., Mara KC; Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN., Meade LA; Anesthesia Clinical Research Unit, Mayo Clinic, Rochester, MN., Paul J; Anesthesia Clinical Research Unit, Mayo Clinic, Rochester, MN., Jannetto PJ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Athreya AP; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN., Scheetz MH; Department of Pharmacy Practice, Chicago College of Pharmacy, Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, IL.; Department of Pharmacy, Northwestern Medicine, Chicago, IL.
Jazyk:	angličtina
Zdroj:	Critical care explorations [Crit Care Explor] 2023 Dec 14; Vol. 5 (12), pp. e1011. Date of Electronic Publication: 2023 Dec 14 (Print Publication: 2023).
DOI:	10.1097/CCE.0000000000001011
Abstrakt:	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. Competing Interests: Dr. Scheetz declares a consultancy with DoseMe. The remaining authors have disclosed that they do not have any potential conflicts of interest. (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)
Databáze:	MEDLINE
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