Voriconazole Pharmacokinetics and Pharmacodynamics in Children

  • Neely M
  • Rushing T
  • Kovacs A
 et al. 
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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 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.

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  • Michael Neely

  • Teresa Rushing

  • Andrea Kovacs

  • Roger Jelliffe

  • Jill Hoffman

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