title: Pharmacokinetics of Posaconazole Oral Suspension in Children Dosed According to Body Surface Area.
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 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 (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 tid results in adequate posaconazole plasma exposure, without significant adverse events.
authors.affiliation: From the *Clinical Pharmacology and Pharmacotherapy, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven, Leuven, Belgium; †Pediatric Department, Fundeni Clinical Institute; ‡Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; §Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences; and ¶Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Kim
authors.initials: K
authors.lastname: Vanstraelen
authors.forename: Anca
authors.initials: A
authors.lastname: Colita
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Bica
authors.forename: Raf
authors.initials: R
authors.lastname: Mols
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.forename: Nele
authors.initials: N
authors.lastname: Peersman
authors.forename: Pieter
authors.initials: P
authors.lastname: Vermeersch
authors.forename: Pieter
authors.initials: P
authors.lastname: Annaert
authors.forename: Isabel
authors.initials: I
authors.lastname: Spriet
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001830:Body Surface Area; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D008297:Male; D009181:Mycoses / Q000517:prevention & control; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D013535:Suspensions / Q000008:administration & dosage*; D014230:Triazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D013535:Suspensions; D014230:Triazoles; C101425:posaconazole