NCT03643497

Population Pharmacokinetics of Meropenem and Linezolid in Children With Severe Infectious Diseases

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 800 (estimated)
• Sponsor: Beijing Children's Hospital · Academic / Other
• Sex: All
• Age: 1 Day – 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

1.Establish population pharmacokinetic (PPK) models of meropenem and linezolid in severe infectious children by nonlinear mixed effect modeling (NONMEM). 1. 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. 2. Plasma and cerebrospinal fluid samples will be tested by high performance liquid chromatography (HPLC). 3. PPK models of meropenem and linezolid will be established by NONMEM program. 4. 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. 1. 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. 2. 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

Conditions

• Children；Infection

Interventions

Type	Name	Description
DRUG	anti-infective drugs	According to the models of population pharmacokinetics, the investigators and want to correlate use of antibiotics with treatment effectiveness and safety in children

Timeline

• Start date: 2018-07-01
• Primary completion: 2021-09-30
• Completion: 2021-12-31
• First posted: 2018-08-22
• Last updated: 2018-08-23

Locations

1 site across 1 country: China