Population Pharmacokinetics of Anti-infective Drugs in Children in Anti-infectious Therapies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 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 anti-infective drugs in children are different from adults. We aim to study the population pharmacokinetics of children receiving the anti-infective drugs for treatment of infectious diseases. In this study, we will detect drug concentration in plasma by using residual blood samples of blood gas analysis and other clinical tests and employ computers for constructing population pharmacokinetic models. In addition, we also want to correlate use of anti-infective drugs with treatment effectiveness and incidence of adverse effects in children. This novel knowledge will allow better and more rational approaches to the treatment of infectious diseases in children. It will also set the foundation for further studies to improve anti-infective drug therapies for children.
详细描述
1.Establish population pharmacokinetic (PPK) models of each anti-infective drug in children by nonlinear mixed effect modeling (NONMEM).
- At different timepoint after antibiotic administration, plasma samples of 100 children will be collected from neonatal intensive care unit (NICU) and pneumology department for each drug. The clinical information includes demography, medication, concentration data, blood biochemical parameters and so on .
- Plasma samples will be tested by high performance liquid chromatography (HPLC).
- PPK models of antibiotics will be established by NONMEM program.
- The reliability and stability of the PPK model will be evaluated by 1000 times of Bootstrap procedure and normalized predictive distribution error (NPDE).
2.Evaluation of the clinical feasibility and safety of individualized dosing.
- According the results of PPK models, we will use dosages recommended in models to cure children infectious diseases in prospective studies. For each antibiotic, 50 children will be collected.
- We will compare the therapeutic effects and safety between children with conventional therapies and children with individualized therapies, including proportions of children with effective drug concentration, improvement speed of of children, liver and kidney functions of 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 infectious diseases.
- •The anti-infective therapy includes drugs commonly used in children infectious diseases, for example, cephalosporins (such as latamoxef, ceftazidime, ceftriaxone and so on), penicillins (such as penicillin, amoxicillin, ampicillin and so on), macrolides (such as erythromycin, azithromycin and so on), carbapenems (sucn as meropenem, imipenem and so on) and antiviral drugs (such as ganciclovir, acyclovir and so on).
- •Children infectious diseases include pneumonia, sepsis, purulent meningitis and other diseases with 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 anti-infective drugs.
- •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
干预措施: cephalosporins,penicillins,macrolides,carbapenems and antiviral 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
- absorption rate constant (ka)(up to 4 weeks)
- elimination rate constant (kel)(up to 4 weeks)
- time to achieve maximum concentration (Tmax)(up to 4 weeks)
- half-life (t1/2)(up to 4 weeks)
研究者
Adong Shen
Deputy Chief of China National Clinical Research Center for Respiratory Diseases
Beijing Children's Hospital