Fluconazole loading dose pharmacokinetics and safety in infants
Lauren Piper1, P Brian Smith, Christoph P Hornik
1Department of Pediatrics and Duke Clinical Research Institute, Duke University, Durham, NC, USA.
The Pediatric Infectious Disease Journal
|November 19, 2010
Summary
A fluconazole loading dose (25 mg/kg) is safe for infants at risk for invasive fungal infection. This dosing strategy rapidly achieves therapeutic fluconazole targets, improving outcomes in candidemic infants.
Area of Science:
- Pediatric pharmacology
- Infectious diseases
- Critical care medicine
Background:
- Invasive candidiasis poses a significant threat to critically ill infants, leading to high morbidity and mortality.
- Achieving a therapeutic fluconazole target (AUC0-24h >400 mg*h/L) is crucial for improving outcomes in candidemic patients.
- A fluconazole loading dose is recommended for adults but its use in infants remains unevaluated.
Purpose of the Study:
- To assess the pharmacokinetics and safety of a fluconazole loading dose in infants.
- To determine if a loading dose helps achieve therapeutic fluconazole targets faster in infants.
Main Methods:
- An open-label study enrolled 10 infants (age <60 days) with suspected systemic fungal infection.
- Nine infants received a 25-mg/kg fluconazole loading dose, followed by 12 mg/kg daily for 4 days.
- Pharmacokinetic indices were estimated using a 1-compartment model with plasma samples collected post-loading and at steady-state.
Main Results:
- Data from 8 infants showed a median fluconazole AUC0-24h of 479 mg*h/L.
- 63% of infants achieved the therapeutic target on the first day of loading dose administration.
- All infants reached a fluconazole 24-hour trough concentration >8 microg/mL, with no drug-related adverse events.
Conclusions:
- A 25-mg/kg fluconazole loading dose is safe in young infants.
- This loading dose regimen allows for more rapid achievement of therapeutic fluconazole targets compared to traditional dosing in infants.
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