Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis

Обзор

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.

Подробное описание

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

1. 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 . 2. Plasma samples will be tested by high performance liquid chromatography (HPLC). 3. PPK models of anti-tuberculsis drug 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 TB children in prospective studies. For anti-tuberculsis 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, 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.

Вмешательства

• Препарат anti-tuberculosis drug
  The intervention drugs are prescribed by treating caregiver

Первичные конечные точки

• maximum concentration (Cmax) [Срок оценки: up to 4 weeks]

Вторичные конечные точки (4)

• time to achieve maximum concentration (Tmax) [Срок оценки: up to 4 weeks]
• absorption rate constant (ka) [Срок оценки: up to 4 weeks]
• elimination rate constant (kel) [Срок оценки: up to 4 weeks]
• half-life (t1/2) [Срок оценки: up to 4 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• Beijing Children's Hospital of Capital Medical University — Пекин

Публикации

• Jacqz-Aigrain E, Leroux S, Zhao W, van den Anker JN, Sharland M. How to use vancomycin optimally in neonates: remaining questions. Expert Rev Clin Pharmacol. 2015;8(5):635-48. doi: 10.1586/17512433.2015.1060124. Epub 2015 Aug 4. PMID 26289222
• Ho PL, Lo PY, Chow KH, Lau EH, Lai EL, Cheng VC, Kao RY. Vancomycin MIC creep in MRSA isolates from 1997 to 2008 in a healthcare region in Hong Kong. J Infect. 2010 Feb;60(2):140-5. doi: 10.1016/j.jinf.2009.11.011. Epub 2009 Dec 2. PMID 19961873
• Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med. 2003 Sep 18;349(12):1157-67. doi: 10.1056/NEJMra035092. No abstract available. PMID 13679531

Идентификаторы

NCT: NCT03625739 · BCH_PPK003

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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