TY - JOUR
T1 - Highly variable plasma concentrations of voriconazole in pediatric hematopoietic stem cell transplantation patients
AU - Bartelink, Imke H.
AU - Wolfs, Tom
AU - Jonker, Martine
AU - De Waal, Marjolein
AU - Egberts, Toine C.G.
AU - Ververs, Tessa T.
AU - Boelens, Jaap J.
AU - Bierings, Marc
N1 - Copyright: Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/1
Y1 - 2013/1
N2 - Invasive fungal infections are of great concern in pediatric hematopoietic stem cell transplantation (HSCT) recipients. Voriconazole is usually the drug of first choice for treating or preventing invasive aspergillosis. Optimum trough levels (Ctroughs) are between 1 and 5 mg/liter. It is unclear whether these levels are reached with currently advised pediatric dosing schedules. Between 2007 and 2011, 11 patients <2 years of age, 31 between 2 and 12 years, and 20 between 12 and 20 years were (prophylactically or therapeutically) treated with voriconazole in the HSCT unit of UMC Utrecht. For children <2 years of age, the dosage recommended for 2 to 12 years was used. In 34% of children who started with the recommended dose, an adequate Ctrough was reached irrespective of age or administration route. After therapeutic drug monitoring (TDM)-based dose adjustments, adequate Ctroughs were reached in 80% of the patients at median doses of 31.5 (age, <2 years), 16 (age, 2 to 12 years), and 9.4 mg/kg of body weight/day (age, >12 years) (P = 0.034). The intrapatient variability in Ctrough ranged between 1 and 238%. Voriconazole was discontinued in six patients due to toxicity. These patients had a median Ctrough of 0.5 mg/liter at the initial dose (ranging from 0.5 to 2.6 mg/liter), and a medium maximal concentration of 4 mg/liter was reached. Inter- and intrapatient variability is a major concern in voriconazole treatment and necessitates therapeutic drug monitoring of dosing, especially in young children.
AB - Invasive fungal infections are of great concern in pediatric hematopoietic stem cell transplantation (HSCT) recipients. Voriconazole is usually the drug of first choice for treating or preventing invasive aspergillosis. Optimum trough levels (Ctroughs) are between 1 and 5 mg/liter. It is unclear whether these levels are reached with currently advised pediatric dosing schedules. Between 2007 and 2011, 11 patients <2 years of age, 31 between 2 and 12 years, and 20 between 12 and 20 years were (prophylactically or therapeutically) treated with voriconazole in the HSCT unit of UMC Utrecht. For children <2 years of age, the dosage recommended for 2 to 12 years was used. In 34% of children who started with the recommended dose, an adequate Ctrough was reached irrespective of age or administration route. After therapeutic drug monitoring (TDM)-based dose adjustments, adequate Ctroughs were reached in 80% of the patients at median doses of 31.5 (age, <2 years), 16 (age, 2 to 12 years), and 9.4 mg/kg of body weight/day (age, >12 years) (P = 0.034). The intrapatient variability in Ctrough ranged between 1 and 238%. Voriconazole was discontinued in six patients due to toxicity. These patients had a median Ctrough of 0.5 mg/liter at the initial dose (ranging from 0.5 to 2.6 mg/liter), and a medium maximal concentration of 4 mg/liter was reached. Inter- and intrapatient variability is a major concern in voriconazole treatment and necessitates therapeutic drug monitoring of dosing, especially in young children.
UR - http://www.scopus.com/inward/record.url?scp=84872028587&partnerID=8YFLogxK
U2 - https://doi.org/10.1128/AAC.01540-12
DO - https://doi.org/10.1128/AAC.01540-12
M3 - Article
C2 - 23114771
SN - 0066-4804
VL - 57
SP - 235
EP - 240
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 1
ER -