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Updated in 2019/5/7 上午 11:12:19      Viewed: 24 times      (Journal Article)
The Pediatric infectious disease journal 30 (5): 375-8 (2011)

Fluconazole loading dose pharmacokinetics and safety in infants.

Lauren Piper , P Brian Smith , Christoph P Hornik , Ira M Cheifetz , Jeffrey S Barrett , Ganesh Moorthy , William W Hope , Kelly C Wade , Michael Cohen-Wolkowiez , Daniel K Benjamin
ABSTRACT
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.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.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 >8 μg/mL. No adverse events were thought to be related to fluconazole therapy.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.
DOI: 10.1097/INF.0b013e318202cbb3      ISSN: 0891-3668