Oral Antibiotic Pharmacokinetics in Young Infants

Characterizing Absorption Kinetics of Oral Antibiotics in Young Infants to Enhance Precision Dosing

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Linezolid; Pharmacokinetic Analysis; Infant and Young Children; Linezolid Pharmacokinetics in Young Infants
• Intervention / Treatment: Drug: Linezolid (LZD)

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, Denver
      • Contact: Andrew S Haynes, MD; Phone Number: 720-777-6783; Email: andrew.haynes@childrenscolorado.org
      • Principal Investigator: Andrew S Haynes, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group 1: Routine Clinical Linezolid; Participants receiving linezolid as part of routine clinical care will undergo pharmacokinetic blood sampling and clinical data collection.
Experimental: Group 2: Single Study Dose of Linezolid; Participants will receive a single study-administered dose of linezolid (10 mg/kg/dose enterally) followed by pharmacokinetic blood sampling and clinical data collection.	Drug: Linezolid (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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	From 0 to 12 hours after administration of an enteral linezolid dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	From signing the informed consent form through study completion, up to 5 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between PBPK model predicted and observed linezolid plasma concentrations	PBPK model predicted plasma linezolid concentrations will be compared with observed plasma linezolid concentrations collected at prespecified sampling time points. Predictive performance will be summarized using the ratio of predicted to observed concentrations.	From 0 to 12 hours after administration of an enteral linezolid dose

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: August 6, 2026
• First Submitted That Met QC Criteria: September 8, 2026
• First Posted (Actual): September 11, 2026

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: pharmacokinetics; infant; neonate; linezolid; oral antibiotic
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Acids, Acyclic; Carboxylic Acids; Amides; Acetamides; Acetates; Oxazolidinones; Oxazoles; Linezolid
• Other Study ID Numbers: 26-1733

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No