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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
Summary
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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