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Voriconazole pharmacokinetics and pharmacodynamics in children

Michael Neely1, Teresa Rushing, Andrea Kovacs

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

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|December 3, 2009
PubMed

Insights

In children, a voriconazole trough concentration above 1000 ng/mL is linked to better survival. Pharmacokinetic variability necessitates monitoring serum voriconazole levels for optimal treatment.

Area of Science:

  • Pediatric Pharmacology
  • Antifungal Pharmacokinetics and Pharmacodynamics

Background:

  • Limited pharmacokinetic and pharmacodynamic data exist for voriconazole in pediatric populations.
  • Understanding voriconazole's behavior in children is crucial for effective treatment of fungal infections.

Purpose of the Study:

  • To investigate the pharmacokinetic variability of voriconazole in children.
  • To determine the pharmacodynamic relationship between serum voriconazole concentrations and clinical outcomes, including survival and toxicity.
  • To inform optimal dosing strategies for pediatric patients.

Main Methods:

  • Retrospective review of patient records at Childrens Hospital Los Angeles.
  • Analysis of demographic data, dosing history, and serum voriconazole concentrations.
  • Application of a 2-compartment Michaelis-Menten pharmacokinetic model to assess variability.

Main Results:

  • A total of 207 voriconazole measurements were analyzed from 46 pediatric patients.
  • A trough serum voriconazole concentration below 1000 ng/mL was significantly associated with increased odds of death (2.6-fold).
  • No association was found between serum voriconazole concentrations and hepatotoxicity; significant pharmacokinetic variability was observed, especially with enteral dosing.

Conclusions:

  • A voriconazole trough concentration exceeding 1000 ng/mL is pharmacodynamically associated with improved survival in children.
  • Significant pharmacokinetic variability, particularly with enteral administration, supports the routine measurement of serum voriconazole concentrations.
  • Simulations suggest specific IV and oral doses may achieve target concentrations, but with considerable inter-patient variability.
Abstract

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