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Pharmacokinetics of rifapentine in children
Michael J Blake1, Susan M Abdel-Rahman, Richard F Jacobs
1Department of Pediatrics, University of Missouri-Kansas City, School of Medicine, USA.
Insights
Pediatric pharmacokinetic studies of rifapentine (a tuberculosis antibiotic) are lacking. This study found that children require higher weight-normalized doses than adults for comparable drug exposure.
Area of Science:
- Pharmacology
- Pediatric Infectious Diseases
- Drug Metabolism
Background:
- Rifapentine is a crucial rifamycin antibiotic for treating Mycobacterium tuberculosis pulmonary infections.
- Existing pharmacokinetic data for rifapentine primarily includes adolescents and adults, with a gap in pediatric and infant research.
Purpose of the Study:
- To assess the pharmacokinetics of rifapentine in children.
- To determine appropriate dosing for pediatric tuberculosis treatment.
Main Methods:
- An open-label study involving 24 children (aged 7.1 ± 3.3 years) receiving single oral doses of rifapentine (150 mg or 300 mg based on weight).
- Serial blood sampling for 32 hours to quantify rifapentine and its metabolite, 25-desacetyl rifapentine, using high-performance liquid chromatography.
- Pharmacokinetic parameters were calculated using a model-independent approach.
Main Results:
- Dose-normalized exposure (AUC) differed significantly between the 150 mg and 300 mg groups, influenced by age.
- Further age-dependent variations in rifapentine exposure and elimination were noted when comparing with adult data.
- Reported adverse events were mild, including gastric distress and vomiting.
Conclusions:
- Rifapentine exposure is lower in children compared to adults at comparable weight-normalized doses.
- A higher weight-normalized (mg/kg) dose of rifapentine is recommended for pediatric patients.
- This finding is critical for optimizing tuberculosis treatment regimens in children.
Background:
Rifapentine is a rifamycin antibiotic approved for the treatment of pulmonary infections caused by Mycobacterium tuberculosis. Although the pharmacokinetics of rifapentine has been investigated in adolescents and adults, no studies have assessed the pharmacokinetics of this drug in children or infants.
Methods:
Twenty-four children (7.1 +/- 3.3 years; mean +/- 1 SD, 27.9 +/- 11.9 kg) were enrolled in this open label study. Children received a single oral dose (10 to <30 kg body weight received 150 mg; 30 to <60 kg body weight received 300 mg), followed by repeated blood sampling (n = 11) for 32 hours. Rifapentine and 25-desacetyl rifapentine were quantitated by a validated high-pressure liquid chromatography method. Pharmacokinetic parameters were determined using a model-independent approach.
Results:
A significant difference in dose-normalized area under the curves (AUC0-n and AUC0-infinity) was observed between children receiving the 150 and 300 mg doses, which was accounted for by differences in age between the dosing arms. In separate analyses, including data from adults, further age-dependence in total body exposure (reflected by AUC) and elimination was observed. Adverse events associated with rifapentine were mild and included gastric distress (n = 1) and vomiting (n = 2).
Conclusions:
Given a comparable weight-normalized dose, rifapentine exposure estimates are lower in children than those reported in adults, suggesting that a larger weight-normalized (ie, mg/kg) dose of rifapentine is needed in children.
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