Pharmacokinetics of Posaconazole Oral Suspension in Children Dosed According to Body Surface Area.

Background: Antifungal prophylaxis remains challenging in immunocompromised children as no clear consensus has yet been reached about which drug to be used. Posaconazole has a broad spectrum of activity, a favorable safety profile and excellent prophylactic activity in adults. However, a lack of pharmacokinetic studies in pediatric patients hampers routine implementation. This study investigates the pharmacokinetics of a newly introduced posaconazole dosing regimen based on the body surface area in pediatric hematologic patients. Methods: In this prospective pharmacokinetic study, 8 blood samples were taken during 1 dosing interval at steady state in children aged 13 years or younger with hematologic malignancy, who were treated prophylactically with posaconazole oral suspension at a dose of 120mg/m(2) 3 times daily. Posaconazole plasma concentrations were determined using high-performance liquid chromatography fluorescence detection. Results: One hundred twelve samples were taken from 14 patients with a mean age of 6.72.8 years. A median posaconazole daily dose of 100.0mg (77.3-100.0) 3 times daily (tid), corresponding to a median of 117.9mg/m(2) (112.2-120.4) tid, resulted in mean trough posaconazole plasma concentrations of 0.85 +/- 0.56mg/L. Pharmacokinetic analysis revealed a clearance of 0.8L/(h kg) (0.5-1.4). No invasive fungal infections or adverse events were encountered during treatment. Conclusions: Posaconazole is a promising antifungal agent to be used prophylactically in hematologic patients aged 13 years or younger. Administering posaconazole oral suspension in a dosage of 120mg/m(2) tid results in adequate posaconazole plasma exposure, without significant adverse events.