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Highly variable plasma concentrations of voriconazole in pediatric hematopoietic stem cell transplantation patients.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2013 Jan; Vol. 57 (1), pp. 235-40. Date of Electronic Publication: 2012 Oct 31. - Publication Year :
- 2013
-
Abstract
- 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 (C(trough)s) 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 C(trough) was reached irrespective of age or administration route. After therapeutic drug monitoring (TDM)-based dose adjustments, adequate C(trough)s 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 C(trough) ranged between 1 and 238%. Voriconazole was discontinued in six patients due to toxicity. These patients had a median C(trough) 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.
- Subjects :
- Adolescent
Analysis of Variance
Antifungal Agents pharmacokinetics
Antifungal Agents pharmacology
Aspergillosis drug therapy
Aspergillosis microbiology
Aspergillosis prevention & control
Aspergillus drug effects
Aspergillus growth & development
Child
Child, Preschool
Drug Administration Schedule
Drug Dosage Calculations
Female
Humans
Infant
Male
Pyrimidines pharmacokinetics
Pyrimidines pharmacology
Treatment Outcome
Triazoles pharmacokinetics
Triazoles pharmacology
Voriconazole
Young Adult
Antifungal Agents blood
Aspergillosis blood
Drug Monitoring
Hematopoietic Stem Cell Transplantation
Pyrimidines blood
Triazoles blood
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 57
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 23114771
- Full Text :
- https://doi.org/10.1128/AAC.01540-12