title: Pharmacokinetics of an elevated dosage of micafungin in premature neonates.
abstract: BACKGROUND
  Determining the safety and pharmacokinetics of antifungal agents in neonates is important. A previous single-dose pharmacokinetic study of micafungin in neonates demonstrated that doses of 0.75 to 3 mg/kg produced lower plasma micafungin concentrations than in older patients because of increased apparent plasma clearance of micafungin in neonates. The primary objective of this study was to assess the safety and pharmacokinetics of an increased (15 mg/kg/d) dose of micafungin.
  
  
  METHODS
  A repeated dose, open-label pharmacokinetic, and safety trial of intravenous micafungin in 12 preterm neonates >48 hours of life with suspected systemic infections. Neonates received 15 mg/kg/d of micafungin for 5 days. Blood samples were drawn relative to either the fourth or fifth dose. Systemic exposure was assessed by examination of the plasma area under the curve.
  
  
  RESULTS
  The median birth weight and gestational age of the neonates were 775 g and 27 weeks, respectively. No adverse events related to micafungin were detected. The mean area under the curve and clearance for the cohort was 437.5 microg'h/mL and 0.575 mL/min/kg, respectively. The calculated clearance and volume of distribution for neonates was greater than that observed in older children and adults.
  
  
  CONCLUSIONS
  These data suggest that 15 mg/kg dosing in premature neonates corresponds to an exposure of approximately 5 mg/kg in adults. No adverse events related to micafungin were observed.
authors.affiliation: Department of Pediatrics and Duke Clinical Research Institute, Duke University, Durham, NC 27715, USA. brian.smith@duke.edu
authors.forename: P Brian
authors.initials: PB
authors.lastname: Smith
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
authors.forename: William
authors.initials: W
authors.lastname: Hope
authors.forename: Antonio
authors.initials: A
authors.lastname: Arrieta
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Takada
authors.forename: Laura L
authors.initials: LL
authors.lastname: Kovanda
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kearns
authors.forename: David
authors.initials: D
authors.lastname: Kaufman
authors.forename: Taiji
authors.initials: T
authors.lastname: Sawamoto
authors.forename: Donald N
authors.initials: DN
authors.lastname: Buell
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Benjamin