Pharmacokinetics and Safety of Micafungin in Infants Supported with Extracorporeal Membrane Oxygenation

Julie Autmizguine, Christoph P. Hornik, Daniel K. Benjamin, Kim L.R. Brouwer, Susan R. Hupp, Michael Cohen-Wolkowiez, Kevin M. Watt

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background: Candida is a leading cause of infection in infants on extracorporeal membrane oxygenation (ECMO). Optimal micafungin dosing is unknown in this population because ECMO can alter drug pharmacokinetics (PK). Methods: To characterize micafungin pharmacokinetics and safety in infants on ECMO, we conducted an open-label pharmacokinetics trial. Infants on ECMO either received intravenous micafungin 4 mg/kg every 24 h for invasive candidiasis prophylaxis or 8 mg/kg every 24 h when a fungal infection was suspected or confirmed. We collected plasma samples after single and multiple micafungin doses. We defined the therapeutic target as the adult exposure associated with efficacy in phase III trials and the prophylactic target as one-half of the therapeutic target. Results: We enrolled 12 infants (124 samples) with a median age of 59 days. Using a 1-compartment model, median weight-normalized volume of distribution and clearance were 0.64 L/kg and 0.041 L/kg/h, respectively. Dose-exposure simulations revealed that doses of 2.5 and 5 mg/kg every 24 h matched exposure targets for prophylaxis and treatment of invasive candidiasis, respectively. We did not observe any drug-related adverse events. Conclusions: In infants on ECMO, micafungin volume of distribution was higher and clearance was in the upper range of previously published values for infants not on ECMO. Based on these data, we recommend dosing of 2.5 and 5 mg/kg every 24 h for prophylaxis and treatment of invasive candidiasis, respectively, to match adult exposure proven effective against Candida spp.

Original languageEnglish (US)
Pages (from-to)1204-1210
Number of pages7
JournalPediatric Infectious Disease Journal
Volume35
Issue number11
DOIs
StatePublished - Nov 1 2016

Keywords

  • Candida prophylaxis
  • Candida therapy
  • antifungal
  • extracorporeal membrane oxygenation
  • infants
  • micafungin
  • pharmacokinetics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

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