title: Safety and pharmacokinetics of repeat-dose micafungin in young infants.
abstract: Given the risk of central nervous system infection, relatively high weight-based echinocandin dosages may be required for the successful treatment of invasive candidiasis and candidemia in young infants. This open-label study assessed the safety and pharmacokinetics (PK) of micafungin in 13 young infants (>48 h and <120 days of life) with suspected candidemia or invasive candidiasis. Infants of body weight > or =1,000 and <1,000 g received 7 and 10 mg/kg/day, respectively, for a minimum of 4-5 days. In the 7-mg/kg/day group, the mean baseline weight and gestational age were 2,101 g and 30 weeks, respectively; in the 10-mg/kg/day group, they were 688 g and 25 weeks, respectively. The median pharmacokinetic values for the 7- and 10-mg/kg/day groups, respectively, were as follows: area under the concentration-time curve from 0 to 24 h (AUC(0-24)), 258.1 and 291.2 microg x h/ml; clearance at steady state adjusted for body weight, 0.45 and 0.57 ml/min/kg; maximum plasma concentration, 23.3 and 24.9 micro g/ml; and volume of distribution at steady state adjusted for body weight, 341.4 and 542.8 ml/kg. No deaths or discontinuations from treatment occurred. These data suggest that micafungin dosages of 7 and 10 mg/kg/day are well tolerated and provide exposure levels that have been shown (in animal models) to be adequate for central nervous system coverage.
authors.affiliation: Department of Pediatrics and Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA. danny.benjamin@duke.edu
authors.forename: D K
authors.initials: DK
authors.lastname: Benjamin
authors.forename: P B
authors.initials: PB
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Arrieta
authors.forename: L
authors.initials: L
authors.lastname: Castro
authors.forename: P J
authors.initials: PJ
authors.lastname: Sánchez
authors.forename: D
authors.initials: D
authors.lastname: Kaufman
authors.forename: L J
authors.initials: LJ
authors.lastname: Arnold
authors.forename: L L
authors.initials: LL
authors.lastname: Kovanda
authors.forename: T
authors.initials: T
authors.lastname: Sawamoto
authors.forename: D N
authors.initials: DN
authors.lastname: Buell
authors.forename: W W
authors.initials: WW
authors.lastname: Hope
authors.forename: T J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000367:Age Factors; D002177:Candidiasis / Q000097:blood / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D054714:Echinocandins / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D055666:Lipopeptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D000077551:Micafungin
chemical_list: D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin