Journal Article

Voriconazole Pharmacokinetics and Pharmacodynamics in Children

Michael Neely, Teresa Rushing, Andrea Kovacs, Roger Jelliffe and Jill Hoffman

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 50, issue 1, pages 27-36
Published in print January 2010 | ISSN: 1058-4838
Published online January 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/648679
Voriconazole Pharmacokinetics and Pharmacodynamics in Children

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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 ⩾ 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 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.

Journal Article.  5132 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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