title: Posaconazole plasma concentrations in pediatric patients receiving antifungal prophylaxis during neutropenia.
abstract: Invasive fungal infections are one of the major complications in pediatric patients during prolonged neutropenia after chemotherapy. Evaluation of the efficacy and safety of the triazole posaconazole in these patients is missing. This multicenter survey analyzed trough concentrations of 33 pediatric patients with a median age of 8 years during 108 neutropenic episodes who received prophylactic posaconazole oral suspension. A total of 172 posaconazole trough levels were determined to median 438 ng/ml (range 111-2011 ng/ml; mean 468 ± 244 ng/ml). Age and gender had no influence on posaconazole plasma levels. Posaconazole was not discontinued due to adverse events in any of the patients. Only hepatic parameters significantly increased beyond the upper normal limit to median values of ALT of 87 U/l (P < .0001), and AST of 67 U/l (P < .0001). One patient with a median posaconazole trough concentration of 306 ng/ml experienced an invasive fungal infection. In conclusion, posaconazole was effective, safe and feasible in 33 pediatric patients with neutropenia ≥5 days after chemotherapy. Median posaconazole plasma concentrations were approximately 1.6-fold lower than the recommended plasma level of 700 ng/ml. Larger patient cohorts are needed to evaluate these findings.
authors.affiliation: University Hospital Tübingen, Children's Hospital, Department I - General Paediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Döring
authors.affiliation: University Hospital Tübingen, Children's Hospital, Department I - General Paediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
authors.forename: Karin Melanie
authors.initials: KM
authors.lastname: Cabanillas Stanchi
authors.affiliation: University Medical Center, Würzburg, Department of Infectiology, Oberdürrbacher Straße 6, 97080 Würzburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Klinker
authors.affiliation: University Hospital Tübingen, Children's Hospital, Department I - General Paediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
authors.forename: Melinda
authors.initials: M
authors.lastname: Eikemeier
authors.affiliation: University Hospital Tübingen, Children's Hospital, Department I - General Paediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Feucht
authors.affiliation: Ludwig-Maximilians-University München, Dr. von Hauner'sches Kinderspital, Pediatric Hematology, Oncology and Stem Cell Transplantation, Lindwurmstrasse 4, 80337 Munich, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Blaeschke
authors.affiliation: University Hospital Tübingen, Children's Hospital, Department I - General Paediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
authors.forename: Carl-Philipp
authors.initials: CP
authors.lastname: Schwarze
authors.affiliation: University Hospital Tübingen, Children's Hospital, Department I - General Paediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Ebinger
authors.affiliation: Ludwig-Maximilians-University München, Dr. von Hauner'sches Kinderspital, Pediatric Hematology, Oncology and Stem Cell Transplantation, Lindwurmstrasse 4, 80337 Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.affiliation: University Hospital Tübingen, Children's Hospital, Department I - General Paediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.affiliation: University Medical Center, Würzburg, Department of Infectiology, Oberdürrbacher Straße 6, 97080 Würzburg, Germany.
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Heinz
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018890:Chemoprevention / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009181:Mycoses / Q000517:prevention & control*; D009503:Neutropenia / Q000150:complications*; D010949:Plasma / Q000737:chemistry*; D012189:Retrospective Studies; D012737:Sex Factors; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole
keywords: invasive fungal infections; leukemia; neutropenia; pediatric patients; posaconazole