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 μg′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.
From the *Department of Pediatrics and Duke Clinical Research Institute, Duke University, Durham, NC; †National Cancer Institute, Bethesda, MD; ‡University of Manchester, Manchester, United Kingdom; §Children’s Hospital of Orange County, CA; ¶Astellas Pharmaceuticals Inc., Tokyo, Japan; ∥Astellas Pharma US, Inc., Deerfield, IL; **Department of Pediatrics and Division of Pediatric Pharmacology and Medical Toxicology, Children’s Mercy Hospital, University of Missouri-Kansas City, Kansas City, MO; and ††Department of Pediatrics, University of Virginia, Charlottesville, VA.
Accepted for publication October 13, 2008.
Supported by Astellas Pharma US, Inc, Deerfield, IL, and in part by grant 5U10HD045962-04, Network of Pediatric Pharmacology Research Units, National Institutes of Health/National Institute for Child Health and Human Development (NIH/NICHD), Bethesda, MD. Support also provided by NIH-1K23HD060040-01.
Address for correspondence: P. Brian Smith, MD, MHS, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715. E-mail: firstname.lastname@example.org.
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