Linezolid Pharmacokinetics in Young Infants, Pharmacokinetic Analysis, Linezolid, Infant and Young Children
Conditions
Keywords
linezolid, pharmacokinetics, neonate, infant, oral antibiotic
Brief summary
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.
Detailed description
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.
Interventions
DRUGLinezolid (LZD)
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.
Sponsors
University of Colorado, Denver
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Days to 90 Days
Healthy volunteers
No
Inclusion criteria
* Hospitalized neonate or young infant ≤90 days postnatal age at screening * Weight ≥2 kg * Receiving systemic antibiotic therapy * Tolerating enteral medication(s) and/or enteral feeds * Group 1: Receiving oral linezolid as part of routine clinical care. * Group 2: Receiving systemic antibiotic therapy but not prescribed linezolid clinically and eligible to receive a single oral study dose.
Exclusion criteria
* Known hypersensitivity or allergy to linezolid * Renal dysfunction (defined by age-appropriate serum creatinine and/or urine output) * Hepatic dysfunction (AST or ALT ≥3x age-specific upper limit of normal or clinically significant hepatic failure) * Gastrointestinal disorders expected to significantly impair drug absorption (e.g., short bowel syndrome, severe malabsorption) * Severe anemia or other condition that precludes study-required blood sampling * Extracorporeal support or other devices expected to substantially alter drug pharmacokinetics (e.g., extracorporeal membrane oxygenation \[ECMO\]). * Therapeutic hypothermia * Ongoing clinical instability that, in the opinion of the treating team or principal investigator (PI), would make study participation unsafe (e.g., escalating vasoactive support or rapidly worsening organ dysfunction).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma linezolid concentration versus time curve from 0 to 24 hours (AUC0-24) | From 0 to 24 hours after administration of an enteral linezolid dose | 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. |
| Apparent clearance of linezolid (CL/F) | From 0 to 12 hours after administration an enteral linezolid dose | 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. |
| Apparent volume of distribution of linezolid (V/F) | From 0 to 12 hours after administration of an enteral linezolid dose | 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. |
| Absorption rate constant of linezolid (Ka) | From 0 to 12 hours after administration of an enteral linezolid dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Linezolid and Primary Metabolites in Plasma | From 0 to 12 hours after administration of an enteral linezolid dose | Measure plasma concentrations of linezolid and its primary metabolites at prespecified sampling time points following routine clinical dosing or a single study dose. |
| Percentage of participants achieving the prespecified linezolid pharmacodynamic target | From 0 to 12 hours after administration of an enteral linezolid dose | 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. |
| Percentage of Participants Experiencing One or More Adverse Events or Serious Adverse Events | From signing the informed consent form through study completion, up to 5 days | 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. |
Countries
United States
Outcome results
None listed