title: Successful empirical antifungal therapy of intravenous itraconazole with pharmacokinetic evidence in pediatric cancer patients undergoing hematopoietic stem cell transplantation.
abstract: OBJECTIVE
  Empirical antifungal therapy prevents invasive fungal infections in patients with cancer. This study assessed the empirical efficacy of intravenous itraconazole in pediatric patients undergoing hematopoietic stem cell transplantation, and investigated the pharmacokinetics and clinical implications.
  
  
  METHODS
  Oral itraconazole syrup was started (2.5 mg/kg twice daily) for prophylaxis, and patients with persistent neutropenic fever for more than 2 days were switched to intravenous itraconazole (5 mg/kg twice daily for 2 days for induction and 5 mg/kg daily for maintenance) as empirical treatment. Empirical antifungal efficacy was assessed retrospectively in 159 transplantations, and a full pharmacokinetic study was prospectively conducted in six of these patients. Successful antifungal efficacy was defined as the fulfillment of all components of a five-part composite end point.
  
  
  RESULTS
  The overall empirical antifungal success rate fulfilling all criteria was 42.1 %. No death or drug-related serious adverse events occurred during the study. Mean trough plasma concentration of itraconazole after oral prophylaxis and intravenous induction were 577.2 and 1659.7 μg/L, respectively. Mean area under the concentration-time curve of itraconazole and its metabolite at steady state were 42,837 ± 24,746 μg·h/L and 63,094 ± 19,255 μg·h/L.
  
  
  CONCLUSIONS
  Intravenous itraconazole was effective and safe as an empirical antifungal agent in pediatric patients; this was due to the fast and satisfactory increase in drug concentration by switching from oral to intravenous therapy.
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, #28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Hyery
authors.initials: H
authors.lastname: Kim
authors.forename: Donghoon
authors.initials: D
authors.lastname: Shin
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Song
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Jang
authors.forename: June Dong
authors.initials: JD
authors.lastname: Park
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.forename: Kyung Duk
authors.initials: KD
authors.lastname: Park
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Shin
authors.forename: Hyo Seop
authors.initials: HS
authors.lastname: Ahn
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D017964:Itraconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D009369:Neoplasms / Q000628:therapy*; D012189:Retrospective Studies
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole