Cefepime pharmacokinetics in critically ill children with multiple organ dysfunction syndrome using volumetric...

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Critical Care Medicine
• Pediatric Pharmacology

Background:

• Multiple organ dysfunction syndrome (MODS) affects up to 50% of critically ill children, increasing mortality.
• Cefepime is a common antibiotic for pediatric sepsis, but its use in MODS lacks pharmacokinetic data.
• Understanding cefepime pharmacokinetics in MODS is crucial for optimizing treatment and improving outcomes.

Purpose of the Study:

• To develop the first population pharmacokinetic (PK) model for cefepime in critically ill children with MODS.
• To evaluate the feasibility of using volumetric absorptive microsampling (VAMS) for PK sampling in this population.
• To establish a basis for optimizing cefepime dosing and monitoring in pediatric MODS.

Main Methods:

• Prospective, observational study of critically ill children with MODS receiving cefepime.
• Collection of up to 15 whole blood samples over 3 days using volumetric absorptive microsampling (VAMS).
• Nonlinear mixed-effects modeling to develop a population PK model, including allometric scaling and covariate analysis (eGFR, age).

Main Results:

• A two-compartment PK model with allometric scaling best described cefepime data.
• Estimated glomerular filtration rate and age were significant covariates on clearance and central volume, respectively.
• PK parameters derived from VAMS data were successfully translated to plasma concentrations, providing estimates for clearance and central volume.

Conclusions:

• The study presents the first population PK model for cefepime in pediatric MODS using VAMS.
• Demonstrates the feasibility of VAMS for PK assessment in critically ill children.
• Provides a foundation for optimizing cefepime therapy and monitoring in this high-risk population.