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Voriconazole pharmacokinetics and safety in immunocompromised children compared to adult patients

Claudia Michael1, Uta Bierbach, Katrin Frenzel

  • 1Institute of Clinical Pharmacology, Faculty of Medicine, University of Leipzig, and University Children's Hospital, Department of Pediatric Hematology and Oncology, Haertelstrasse 16/18, 04107 Leipzig, Germany. Claudia.Michael@medizin.uni-leipzig.de

Antimicrobial Agents and Chemotherapy
|June 16, 2010
PubMed

Insights

This study evaluated voriconazole pharmacokinetics in children and adults. The 7 mg/kg intravenous dose is recommended for children aged 2 to 12 years, showing comparable exposure to adults.

Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Pediatric Infectious Diseases

Background:

  • Systemic fungal infections require effective antifungal therapy.
  • Voriconazole is a broad-spectrum triazole antifungal agent.
  • Understanding voriconazole pharmacokinetics in pediatric populations is crucial for optimizing treatment.

Purpose of the Study:

  • To investigate the pharmacokinetics and safety of intravenous voriconazole in immunocompromised children and adults.
  • To compare voriconazole exposure and variability between pediatric and adult patients.
  • To assess the suitability of the European Medicines Agency-approved intravenous dose for children.

Main Methods:

  • A pharmacokinetic study involving intravenous voriconazole administration in pediatric (2-11 years) and adult (20-60 years) patients.
  • Dosing regimens included 7 mg/kg every 12 hours for pediatric patients and loading doses followed by maintenance doses (5 mg/kg for children, 4 mg/kg for adults) twice daily for others.
  • Blood samples were collected to measure voriconazole trough levels over 10 days and regular levels up to 12 hours postdose on day 3.

Main Results:

  • Wide intra- and interindividual variations in plasma voriconazole levels were observed, particularly in children receiving 7 mg/kg.
  • 56% of pediatric patients on the 7 mg/kg dose had suboptimal trough voriconazole levels (<1 microg/ml or >6 microg/ml).
  • The 7 mg/kg intravenous dose in children resulted in exposure comparable to adults on 4 mg/kg, with higher Cmax values in children; voriconazole exhibited nonlinear pharmacokinetics in most children.

Conclusions:

  • The intravenous dose of 7 mg/kg is recommended for children aged 2 to <12 years for treating systemic fungal infections.
  • Voriconazole therapy was safe and well-tolerated in both pediatric and adult patients.
  • The findings support the current European Medicines Agency-approved intravenous dosing regimen for pediatric voriconazole use.

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