Characterizing Absorption Kinetics of Oral Antibiotics in Young Infants to Enhance Precision Dosing
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Area under the plasma linezolid concentration versus time curve from 0 to 24 hours (AUC0-24)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 0 Days 至 90 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
Group 1: Routine Clinical Linezolid
Participants receiving linezolid as part of routine clinical care will undergo pharmacokinetic blood sampling and clinical data collection.
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.
干预措施: Linezolid (LZD) (Drug)
结局指标
主要结局
Area under the plasma linezolid concentration versus time curve from 0 to 24 hours (AUC0-24)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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.
次要结局
- Concentrations of Linezolid and Primary Metabolites in Plasma(From 0 to 12 hours after administration of an enteral linezolid dose)
- Percentage of participants achieving the prespecified linezolid pharmacodynamic 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(From signing the informed consent form through study completion, up to 5 days)