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Voriconazole Concentrations in Cerebrospinal Fluid During Prophylactic Use in Children with Acute Myelogenous

Ryoji Kobayashi1, Hirozumi Sano, Kenji Kishimoto

  • 1From the Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan.

The Pediatric Infectious Disease Journal
|December 10, 2015
PubMed

Insights

This study analyzed voriconazole (VRCZ) levels in cerebrospinal fluid (CSF) for children with acute myelogenous leukemia. VRCZ transfer into the brain is more efficient at lower plasma concentrations.

Area of Science:

  • Pharmacokinetics
  • Neuroscience
  • Pediatric Oncology

Background:

  • Voriconazole (VRCZ) is a key antifungal agent used in immunocompromised patients.
  • Understanding VRCZ penetration into the central nervous system (CNS) is crucial for managing invasive fungal infections in pediatric leukemia patients.
  • Prophylactic VRCZ use in this population necessitates clear data on its efficacy and safety within the CNS.

Purpose of the Study:

  • To analyze voriconazole (VRCZ) concentrations in cerebrospinal fluid (CSF) during prophylactic use in pediatric patients with acute myelogenous leukemia (AML).
  • To determine the CSF/plasma ratio of VRCZ and identify factors influencing its penetration across the blood-brain barrier (BBB).

Main Methods:

  • Analysis of VRCZ concentrations in paired CSF and plasma samples.
  • Correlation analysis to assess relationships between VRCZ levels, CSF/plasma ratio, age, body weight, and VRCZ concentrations.
  • Statistical evaluation of pharmacokinetic parameters.

Main Results:

  • The median CSF/plasma ratio for VRCZ was 0.57 (range, 0.35-1.04).
  • A significant positive correlation was observed between VRCZ concentrations in CSF and plasma.
  • The CSF/plasma ratio demonstrated a negative correlation with patient age, body weight, and VRCZ concentrations in both CSF and plasma.

Conclusions:

  • Voriconazole (VRCZ) penetrates the CNS in pediatric patients with acute myelogenous leukemia (AML).
  • VRCZ transfer into the CSF is more efficient at lower plasma concentrations, suggesting a saturable or concentration-dependent transport mechanism across the BBB.
  • Further research is needed to elucidate the exact mechanism of VRCZ penetration into the CNS.

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