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.