Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis

Capital Medical University

Status: Enrolling

Conditions: Tuberculosis

Treatments: Drug: anti-tuberculosis drug

Study type: Observational

Funder types: Other

Identifiers

NCT03625739

BCH_PPK003

Details and patient eligibility

About

This study is based on the hypothesis that the pharmacokinetics of anti-tuberculosis drugs in TB children are different from adults. The investigators aim to study the population pharmacokinetics of children receiving the anti-tuberculsis drugs for treatment of TB. In this study, the investigators 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, the investigators also want to correlate use of anti-tuberculsis 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 TB in children. It will also set the foundation for further studies to improve anti-tuberculosis drug therapies for children.

Full description

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

At different timepoint after anti-tuberculsis drug 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 anti-tuberculsis drug 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, the investigators will use dosages recommended in models to cure TB children in prospective studies. For anti-tuberculsis drug, 50 children will be collected. The investigators 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.

Enrollment: 800 estimated patients

Sex: All

Ages: 1 day to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children (0-18 years old) with anti-tuberculosis therapy against TB.
• The anti-tuberculsis therapy includes drugs commonly used in children infectious diseases
• Informed consent signed by the parents and/or guardians.

Exclusion criteria

• Anti-tuberculosis 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-tuberculsis drugs.
• Parents and/or guardians do not agree to participate in this study.