Population Pharmacokinetics of Meropenem and Linezolid in Children With Severe Infectious Diseases
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 800
- 试验地点
- 1
- 主要终点
- maximum concentration (Cmax)
研究概览
简要总结
This study is based on the hypothesis that the pharmacokinetics of meropenem and linezolid in severe infectious children are different from mild infectious children and adults. The investigators aim to study the population pharmacokinetics of children receiving the meropenem and linezolid for treatment of severe infectious diseases. In this study, the investigators will detect drug concentration in plasma and cerebrospinal fluid by using residual blood samples of blood and cerebrospinal fluid gas analysis and other clinical tests and employ computers for constructing population pharmacokinetic models. In addition, the investigators also want to correlate use of meropenem and linezolid with treatment effectiveness and incidence of adverse effects in children. This novel knowledge will allow better and more rational approaches to the treatment of severe infectious diseases in children. It will also set the foundation for further studies to improve anti- infective drug therapies for severe infectious children.
详细描述
1.Establish population pharmacokinetic (PPK) models of meropenem and linezolid in severe infectious children by nonlinear mixed effect modeling (NONMEM).
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At different time point after meropenem or linezolid administration, plasma and/or cerebrospinal fluid samples of 100 children will be collected from pediatric intensive care unit (PICU) for each drug. The clinical information includes demography, medication, concentration data, blood biochemical parameters and so on.
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Plasma and cerebrospinal fluid samples will be tested by high performance liquid chromatography (HPLC).
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PPK models of meropenem and linezolid will be established by NONMEM program.
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The reliability and stability of the PPK model will be evaluated by 1000 times of Bootstrap procedure and normalized predictive distribution error(NPDE).
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Evaluation of the clinical feasibility and safety of individualized dosing.
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According the results of PPK models, the investigators will use dosages recommended in models to cure severe infectious children in prospective studies. For antibiotic drug, 50 children will be collected.
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The investigators will compare the therapeutic effects and safety between children with conventional therapies and children with individualized therapies in severe infectious diseases, including proportions of children with effective drug concentration, improvement speed of children, liver and kidney functions of children, adverse reactions of drugs and so on
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Day 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children (0-18 years old) with anti-infective therapy against severe infectious diseases.
- •The anti-infective therapy includes meropenem and linezolid commonly used in children with infectious diseases,
- •Children severe infectious diseases include severe pneumonia, sepsis, purulent meningitis and other diseases with severe infection.
- •Informed consent signed by the parents and/or guardians
排除标准
- •Anti-infective drugs aren't involved in the therapies of children.
- •It is unable to provide complete medical records or the current condition cannot accept the study process.
- •Patients are allergic to meropenem or linezolid.
- •Parents and/or guardians do not agree to participate in this study.
研究组 & 干预措施
Children with the usage of anti-infective drugs
Children received meropenem or linezolid monotherapy in the treatment of seven infectious diseases
干预措施: anti-infective drugs (Drug)
结局指标
主要结局
maximum concentration (Cmax)
时间窗: up to 4 weeks
Cmax is a term used in pharmacokinetics refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose
次要结局
- time to achieve maximum concentration (Tmax)(up to 4 weeks)
- absorption rate constant (ka)(up to 4 weeks)
- half-life (t1/2)(up to 4 weeks)
- elimination rate constant (kel)(up to 4 weeks)
研究者
Adong Shen
Deputy Chief of China National Clinical Research Center for Respiratory Diseases
Beijing Children's Hospital