title: Poor absorption of high-dose posaconazole in pediatric bone marrow transplant patients.
abstract: OBJECTIVE
  To describe the use of high-dose posaconazole in 2 pediatric patients who received bone marrow transplant (BMT) and highlight concerns regarding posaconazole absorption.
  
  
  METHODS
  We present 2 pediatric BMT patients in whom prescribed high doses of posaconazole (120-300 mg/kg/day for >3 months) provided serum concentrations less than 1 μg/mL. Both patients received posaconazole with other antifungal therapy and surgical debridement for Rhizopus spp. infections after allogeneic BMTs. Various alternative dosing strategies to potentially enhance posaconazole absorption to increase serum concentrations were attempted, including higher daily doses, frequent or continuous oral administration via feeding tube, use of enteral nutrition, and limiting use of acid-blocking agents. During high-dose therapy, frequent posaconazole serum concentration measurement and other monitoring techniques, such as continuous telemetry, were used. While the fungal infections resolved in both patients and no serious adverse effects could be attributed to high-dose posaconazole administration, posaconazole therapy may have contributed to nausea and vomiting in 1 of the patients.
  
  
  CONCLUSIONS
  These 2 cases describe complex circumstances, with several reasons that may have affected the patients' posaconazole serum concentrations. Both patients received significantly higher doses than those recommended in the posaconazole prescribing information, but potentially serious adverse events were not observed since serum concentration measurements were rarely more than 0.5 μg/mL.
  
  
  CONCLUSIONS
  The safety of high-dose posaconazole therapy was not determined in these 2 patients. However, given that limited alternative therapy options are available for severely ill patients with suspected posaconazole malabsorption, research regarding dosing strategies should be considered.
authors.affiliation: Department of Pharmacy Practice & Science, University of Arizona, Tucson, AZ, USA. matthias@pharmacy.arizona.edu
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Matthias
authors.forename: David E
authors.initials: DE
authors.lastname: Nix
authors.forename: Charles A
authors.initials: CA
authors.lastname: Peloquin
authors.forename: Michael L
authors.initials: ML
authors.lastname: Graham
mesh_terms: D000042:Absorption; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002648:Child; D006801:Humans; D007223:Infant; D008297:Male; D009181:Mycoses / Q000188:drug therapy / Q000517:prevention & control; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole