Posaconazole plasma concentration in pediatric patients receiving antifungal prophylaxis after allogeneic hematopoietic stem cell transplantation.
Posaconazole has been proven to be effective for antifungal prophylaxis in adults after hematopoietic stem cell transplantation (HSCT). Due to low gastrointestinal resorption of posaconazole suspension, bioavailability is impaired. Fatty food improves the uptake of posaconazole, but insufficient data on the pharmacokinetics of posaconazole in pediatric patients are available so far. The single-center analysis investigated 161 posaconazole serum concentrations in 27 pediatric patients after HSCT receiving 12 mg·kg BW(-1)·d(-1) posaconazole suspension depending on age, gender, and intestinal graft-versus-host (iGvHD) disease, and the influence of posaconazole on cyclosporine A plasma concentrations. To improve the uptake of posaconazole, one patient cohort received higher fat nutrition with the drug administration. A comparison of the regular nutrition and higher-fat nutrition groups revealed the following values: 31 (27.4%) versus 8 (16.7%) < 500 ng/ml; 12 (10.6%) versus 7 (14.6%) 500-700 ng/ml; 8 (7.1%) versus 6 (12.5%) 700-1000 ng/ml; 51 (45.1%) versus 21 (43.8%) 1000-2000 ng/ml; and 11 (9.7%) versus 6 (12.5%) > 2000 ng/ml. The mean posaconazole concentrations in patients with regular nutrition was 1123 ± 811 ng/ml and with higher-fat nutrition was 1191 ± 673 ng/ml. Posaconazole levels in patients with iGvHD were significantly lower (P = 0.0003) than in patients without GvHD. The majority of samples showed a sufficient posaconazole concentration above 700 ng/ml. Posaconazole levels were slightly higher in patients with higher-fat nutrition and significantly lower in patients with iGvHD. Cyclosporine A levels were not significantly higher during posaconazole administration.
University of Würzburg Medical Center, Department of Internal Medicine II, Oberdürrbacher Straße 6, 97080 Würzburg, Germany.
Werner J
WJ
Heinz
University Hospital Tübingen, Children's Hospital, Department I - General Pediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
Karin M
KM
Cabanillas Stanchi
University of Würzburg Medical Center, Department of Internal Medicine II, Oberdürrbacher Straße 6, 97080 Würzburg, Germany.
Hartwig
H
Klinker
University Hospital Tübingen, Children's Hospital, Department I - General Pediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
Olivia
O
Blume
University Hospital Tübingen, Children's Hospital, Department I - General Pediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
Judith
J
Feucht
University Hospital Tübingen, University Pharmacy, Röntgenweg 9, 72076 Tübingen, Germany.
Ulrike
U
Hartmann
Ludwig-Maximilians-University München, Dr. von Hauner'sches Kinderspital, Pediatric Hematology, Oncology and Stem Cell Transplantation, Lindwurmstrasse 4, 80337 Munich.
Tobias
T
Feuchtinger
University Hospital Tübingen, Children's Hospital, Department I - General Pediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
Peter
P
Lang
University Hospital Tübingen, Children's Hospital, Department I - General Pediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany.
Rupert
R
Handgretinger
University Hospital Tübingen, Children's Hospital, Department I - General Pediatrics, Hematology/Oncology, Hoppe-Seyler-Str.1, 72076 Tübingen, Germany Ludwig-Maximilians-University München, Dr. von Hauner'sches Kinderspital, Pediatric Hematology, Oncology and Stem Cell Transplantation, Lindwurmstrasse 4, 80337 Munich michaela.doering@med.uni-tuebingen.de.
Michaela
M
Döring
D000293:Adolescent; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018890:Chemoprevention / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D004032:Diet / Q000379:methods; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D009181:Mycoses / Q000517:prevention & control*; D010949:Plasma / Q000737:chemistry*; D014184:Transplantation, Homologous / Q000009:adverse effects*; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole
Posaconazole; antifungal prophylaxis; cyclosporine A; graft-versus-host disease; hematopoietic stem cell transplantation; nutrition; pediatric patients