This observational study will characterize the pharmacokinetics of linezolid in young infants. Participants will receive linezolid either as part of routine clinical care or as a single, one-time study dose. Blood samples collected following linezolid administration will be used to measure drug concentrations and describe how linezolid is absorbed, distributed, metabolized, and eliminated in this population. Clinical information, including demographic characteristics, laboratory values, and treatment details, will also be collected. The results will be used to develop pharmacokinetic models to improve linezolid dosing recommendations and support precision dosing in young infants.
Young infants are at increased risk for serious bacterial infections, yet limited pharmacokinetic data are available to guide evidence-based dosing of oral linezolid in this population. Developmental changes in drug absorption, distribution, metabolism, and elimination during early infancy contribute to variability in drug exposure, making it difficult to optimize dosing using existing recommendations. This prospective pharmacokinetic study will enroll young infants who receive linezolid either as part of routine clinical care or as a single, one-time study dose. Blood samples will be collected to measure plasma linezolid concentrations, and demographic, clinical, laboratory, and medication data will be collected from the medical record. These data will be used to develop pharmacokinetic models and evaluate sources of variability in linezolid exposure, including developmental and clinical factors. The results of this study are expected to improve the understanding of oral linezolid pharmacokinetics in young infants and support the development of model-informed dosing strategies to optimize antibiotic exposure, maximize treatment effectiveness, and minimize toxicity in this vulnerable population.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
40
Linezolid is administered either as part of routine clinical care or as a single, one-time study dose (10 mg/kg/dose enterally), depending on study arm. Participants undergo pharmacokinetic blood sampling after linezolid administration to characterize drug disposition in young infants.
University of Colorado, Denver
Aurora, Colorado, United States
Area under the plasma linezolid concentration versus time curve from 0 to 24 hours (AUC0-24)
Area under the plasma linezolid concentration versus time curve from 0 to 24 hours (AUC0-24) will be estimated using plasma linezolid concentrations collected after enteral administration of linezolid (either routine clinical dosing or a single study dose) and pharmacokinetic modeling. AUC0-24 will be reported in mcg hour per mL.
Time frame: From 0 to 24 hours after administration of an enteral linezolid dose
Apparent clearance of linezolid (CL/F)
Apparent clearance of linezolid following enteral administration (either routine clinical dosing or a single study dose) will be estimated from plasma linezolid concentrations using population pharmacokinetic modeling. Apparent clearance will be reported in L/hour.
Time frame: From 0 to 12 hours after administration an enteral linezolid dose
Apparent volume of distribution of linezolid (V/F)
Apparent volume of distribution of linezolid following enteral administration (either routine clinical dosing or a single study dose) will be estimated from plasma linezolid concentrations using population pharmacokinetic modeling. Apparent volume of distribution will be reported in L per kilogram of body weight.
Time frame: From 0 to 12 hours after administration of an enteral linezolid dose
Absorption rate constant of linezolid (Ka)
The absorption rate constant of linezolid following enteral administration (either routine clinical dosing or a single study dose) will be estimated from plasma linezolid concentrations using population pharmacokinetic modeling. The absorption rate constant will be reported in 1/hour.
Time frame: From 0 to 12 hours after administration of an enteral linezolid dose
Concentrations of Linezolid and Primary Metabolites in Plasma
Measure plasma concentrations of linezolid and its primary metabolites at prespecified sampling time points following routine clinical dosing or a single study dose.
Time frame: From 0 to 12 hours after administration of an enteral linezolid dose
Percentage of participants achieving the prespecified linezolid pharmacodynamic target
Pharmacodynamic target attainment will be determined using model-estimated linezolid exposure and a prespecified pharmacodynamic target based on the AUC0-24/MIC ratio. The specific target threshold will be defined in the study analysis plan based on available pharmacodynamic data. The outcome will be reported as the percentage of participants achieving the prespecified target.
Time frame: From 0 to 12 hours after administration of an enteral linezolid dose
Percentage of Participants Experiencing One or More Adverse Events or Serious Adverse Events
Adverse events and serious adverse events will be assessed from signing the informed consent form through study completion, up to 5 days. The incidence, severity, and type of adverse events and serious adverse events will be assessed. The outcome will be reported as the percentage of participants experiencing one or more adverse events or serious adverse events.
Time frame: From signing the informed consent form through study completion, up to 5 days
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