Pharmacokinetics of Posaconazole Oral Suspension in Children Dosed According to Body Surface Area. Issue 2 (February 2016)

• Record Type: Journal Article
• Authors: Vanstraelen, Kim; Colita, Anca; Bica, Ana Maria; Mols, Raf; Augustijns, Patrick; Peersman, Nele; Vermeersch, Pieter; Annaert, Pieter; Spriet, Isabel
• Is Part Of: Pediatric infectious disease journal. Volume 35:Issue 2(2016)
• Publication Date: 2016-02
• Subjects: posaconazole oral suspension -- prophylaxis -- dosing regimen -- body surface area -- pediatrics; Communicable diseases in children -- Periodicals; Infection in children -- Periodicals; 618.929
• DOI: 10.1097/INF.0000000000000963
• Languages: English
• ISSNs: 0891-3668

Abstract

Abstract : 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/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 6.7 ± 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/m 2 (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/m 2 tid results in adequate posaconazole plasma exposure, without significant adverse events. Abstract : Supplemental Digital Content is available in the text.