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Population Pharmacokinetics of Anti-infective Drugs in Children With Infectious Diseases

Recruiting
Conditions
Children; Infection
Interventions
Drug: cephalosporins,penicillins,macrolides,carbapenems and antiviral drugs
Registration Number
NCT03113344
Lead Sponsor
Beijing Children's Hospital
Brief Summary

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.

Detailed Description

1.Establish population pharmacokinetic (PPK) models of each anti-infective drug in children by nonlinear mixed effect modeling (NONMEM).

1. 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 .

2. Plasma samples will be tested by high performance liquid chromatography (HPLC).

3. PPK models of antibiotics 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, we will use dosages recommended in models to cure children infectious diseases in prospective studies. For each antibiotic, 50 children will be collected.

2. 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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
800
Inclusion Criteria
  • 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.
Exclusion Criteria
  • 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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Children with the usage of anti-infective drugscephalosporins,penicillins,macrolides,carbapenems and antiviral drugs-
Primary Outcome Measures
NameTimeMethod
maximum concentration (Cmax)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.

Secondary Outcome Measures
NameTimeMethod
absorption rate constant (ka)up to 4 weeks

Ka is the rate constant of drug absorption.

elimination rate constant (kel)up to 4 weeks

The elimination rate constant is a value used in pharmacokinetics to describe the rate at which a drug is removed from the system.

time to achieve maximum concentration (Tmax)up to 4 weeks

Tmax is the term used in pharmacokinetics to describe the time at which the Cmax is observed.

half-life (t1/2)up to 4 weeks

Half-life is the time required for a quantity to reduce to half its initial value.

Trial Locations

Locations (1)

Beijing Children's Hospital of Capital Medical University

🇨🇳

Beijing, China

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