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 120 mg/m2 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 6.7 ± 2.8 years. A median posaconazole daily dose of 100.0 mg (77.3–100.0) 3 times daily (tid), corresponding to a median of 117.9 mg/m2 (112.2–120.4) tid, resulted in mean trough posaconazole plasma concentrations of 0.85 ± 0.56 mg/L. Pharmacokinetic analysis revealed a clearance of 0.8 L/(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 120 mg/m2 tid results in adequate posaconazole plasma exposure, without significant adverse events.
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 120 mg/m2 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 6.7 ± 2.8 years. A median posaconazole daily dose of 100.0 mg (77.3–100.0) 3 times daily (tid), corresponding to a median of 117.9 mg/m2 (112.2–120.4) tid, resulted in mean trough posaconazole plasma concentrations of 0.85 ± 0.56 mg/L. Pharmacokinetic analysis revealed a clearance of 0.8 L/(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 120 mg/m2 tid results in adequate posaconazole plasma exposure, without significant adverse events.
Keywords: body surface area; dosing regimen; pediatrics; posaconazole oral suspension; prophylaxis
Document Type: Research Article
Publication date: 01 February 2016
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