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Published on: April 5, 2017

Pyrazinamide plasma concentrations in young children with tuberculosis

Helen McIlleron1, Marianne Willemse, Hendrik Simon Schaaf

  • 1Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

The Pediatric Infectious Disease Journal
|March 19, 2011
PubMed

Insights

In children undergoing tuberculosis treatment, pyrazinamide peak plasma concentrations were measured. Lower doses (< 20 mg/kg) were linked to sub-therapeutic pyrazinamide levels (< 20 mg/L) in 15% of pediatric patients.

Area of Science:

  • Pharmacology
  • Pediatrics
  • Infectious Diseases

Background:

  • Tuberculosis remains a significant global health challenge, particularly in pediatric populations.
  • Accurate dosing of antituberculosis drugs like pyrazinamide is crucial for treatment efficacy and preventing drug resistance.
  • Understanding pyrazinamide pharmacokinetics in children is essential for optimizing treatment regimens.

Purpose of the Study:

  • To determine pyrazinamide plasma concentrations in children one month after initiating antituberculosis therapy.
  • To assess the relationship between administered pyrazinamide dose and achieved peak plasma concentrations in pediatric patients.
  • To identify the prevalence of sub-therapeutic pyrazinamide concentrations in this cohort.

Main Methods:

  • Plasma samples were collected from 34 children (median age 3.32 years) one month into antituberculosis treatment.
  • Pyrazinamide plasma concentrations were quantified, focusing on peak levels (Cmax).
  • Dose (mg/kg) and peak concentration (mg/L) data were analyzed to identify trends and correlations.

Main Results:

  • The median peak pyrazinamide concentration was 30.7 mg/L (IQR: 25.5-35.0 mg/L) following a median dose of 23 mg/kg.
  • Five children (15%) exhibited peak concentrations below 20 mg/L, considered potentially sub-therapeutic.
  • Sub-therapeutic pyrazinamide levels were more frequently observed in children who received doses below 20 mg/kg.

Conclusions:

  • A significant proportion of children may not achieve optimal pyrazinamide plasma concentrations with standard dosing regimens.
  • Lowering the pyrazinamide dose below 20 mg/kg increases the risk of sub-therapeutic levels in pediatric tuberculosis patients.
  • Therapeutic drug monitoring and dose adjustments may be necessary to ensure effective pyrazinamide treatment in children.

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