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Medline ® Abstract for Reference 37

of 'Treatment of Candida infection in neonates'

37
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Fluconazole loading dose pharmacokinetics and safety in infants.
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Piper L, Smith PB, Hornik CP, Cheifetz IM, Barrett JS, Moorthy G, Hope WW, Wade KC, Cohen-Wolkowiez M, Benjamin DK Jr
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Pediatr Infect Dis J. 2011;30(5):375.
 
BACKGROUND: Invasive candidiasis is a leading cause of morbidity and mortality in critically ill infants. Prompt administration of fluconazole and achievement of the therapeutic target (area under the curve 0 to 24 hours>400 mg*h/L) improve outcomes in candidemic patients. A loading dose of fluconazole is advised for older patients but has not been evaluated in infants. We sought to determine the pharmacokinetics and safety of a fluconazole loading dose in infants at risk for invasive fungal infection.
METHODS: We enrolled 10 hospitalized infants<60 days old with suspected systemic fungal infection in this open-label study; 9 received a 25-mg/kg fluconazole loading dose followed by a maintenance dose of 12 mg/kg every 24 hours for 4 additional days. Plasma samples were obtained following the loading and steady-state doses (doses 3-5). We used a 1-compartment model to fit the data to estimate pharmacokinetic indices.
RESULTS: Data from 57 drug concentrations obtained from 8 infants (median postnatal age, 16 days [interquartile range, 13-32]and median gestational age, 37 weeks[35-38]) showed that the median fluconazole area under the curve 0 to 24 hours (mg*h/L) in this population was 479 (347-496). Of the 8 infants who received the loading dose, 5 (63%) achieved the therapeutic target on the first day of dosing, and all infants achieved a fluconazole 24-hour trough concentration>8μg/mL. No adverse events were thought to be related to fluconazole therapy.
CONCLUSIONS: A loading dose of fluconazole (25 mg/kg) was safe in this small cohort of young infants and achieved the therapeutic target more rapidly than traditional dosing.
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Department of Pediatrics and Duke Clinical Research Institute, Duke University, Durham, NC, USA.
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