Pharmacokinetics and Safety of Micafungin in Infants Supported With Extracorporeal Membrane Oxygenation.
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.
From the *Department of Pharmacology, University of Montreal, Montreal, Quebec, Canada; †Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina; and ‡Eshelman School of Pharmacy, The University of North Carolina, Chapel Hill, North Carolina.
Julie
J
Autmizguine
Christoph P
CP
Hornik
Daniel K
DK
Benjamin
Kim L R
KL
Brouwer
Susan R
SR
Hupp
Michael
M
Cohen-Wolkowiez
Kevin M
KM
Watt
D019072:Antibiotic Prophylaxis; D000935:Antifungal Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002177:Candidiasis / Q000188:drug therapy / Q000517:prevention & control; D054714:Echinocandins / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D055666:Lipopeptides / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D000077551:Micafungin; D011446:Prospective Studies
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin