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Clin Infect Dis. 2010 Jan 1;50(1):27-36. doi: 10.1086/648679.

Voriconazole pharmacokinetics and pharmacodynamics in children.

Author information

  • 1Division of Pediatric Infectious Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. mneely@usc.edu

Abstract

BACKGROUND:

Voriconazole pharmacokinetic and pharmacodynamic data are lacking in children.

METHODS:

Records at the Childrens Hospital Los Angeles were reviewed for children with > or =1 serum voriconazole concentration measured from 1 May 2006 through 1 June 2007. Information on demographic characteristics, dosing histories, serum concentrations, toxicity and survival, and outcomes was obtained.

RESULTS:

A total of 207 voriconazole measurements were obtained from 46 patients (age, 0.8-20.5 years). A 2-compartment Michaelis-Menten pharmacokinetic model fit the data best but explained only 80% of the observed variability. The crude mortality rate was 28%, and each trough serum voriconazole concentration <1000 ng/mL was associated with a 2.6-fold increased odds of death (95% confidence interval, 1.6-4.8; P=.002). Serum voriconazole concentrations were not associated with hepatotoxicity. Simulations predicted an intravenous dose of 7 mg/kg or an oral dose of 200 mg twice daily would achieve a trough >1000 ng/mL in most patients, but with a wide range of possible concentrations.

CONCLUSIONS:

We found a pharmacodynamic association between a voriconazole trough >1000 ng/mL and survival and marked pharmacokinetic variability, particularly after enteral dosing, justifying the measurement of serum concentrations.

PMID:
19951112
PMCID:
PMC2803104
DOI:
10.1086/648679
[PubMed - indexed for MEDLINE]
Free PMC Article
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