PW-10

J. Autmizguine,1 M. Cohen-Wolkowiez,2 K. L. Brouwer,3 D. K. Benjamin, Jr,2 K. M. Watt2; 1University of Montreal, Montreal, QC, Canada, 2Duke University Medical Center, Durham, NC, 3The University of North Carolina, School of Pharmacy, Chapel Hill, NC

BACKGROUND: Candida is a leading cause of infection-related death in infants on Extracorporeal Membrane Oxygenation. ECMO can alter drug pharmacokinetics (PK) resulting in inadequate drug exposure. We assessed micafungin PK in infants on ECMO.
METHODS: In an open label study, infants on ECMO received IV micafungin 4-8 mg/kg/day for prophylaxis (≤8 days) or treatment per routine medical care. Plasma samples (n=14) were collected around dose 1 and 4. PK was analyzed by compartmental analysis (Phoenix v6.3). Area under the concentration-time curves 0-24 h (AUC) after dose 1 and 4 were compared to adult exposure recommended for treatment (AUC=95 mg*h/L) or prevention (AUC=47.5 mg*h/L) of candidiasis.
RESULTS: Eight infants (90 samples) received a median (range) dose of 4 (4, 8) mg/kg/day. Median age and weight were 56 (0, 574) days and 3.7 (2.9, 9.6) kg, respectively. A one-compartment model fit the data well (CV<15%, Table). All subjects achieved the prophylaxis target after dose 1 and 4; 5/8 (63%) and 3/6 (50%) infants did not achieve therapeutic target after dose 1 and 4, respectively.
CONCLUSION: Infants on ECMO had higher volume of distribution but similar clearance compared to infants not on ECMO (historical controls). Micafungin doses of 4 mg/kg/day in this cohort provided adequate exposure for candidiasis prophylaxis, but higher doses may be required for treatment.

Pharmacokinetic parameters

Subject ID Age
(days)
Clearance
(L/h/kg)
Volume of distribution
(L/kg)
Dose 1
AUC0-24
(h*mg/L)
(normalized for micafungin dosing of 4 mg/kg)
Dose 4
AUC0-24
(h*mg/L)
(normalized for micafungin dosing of 4 mg/kg)
1 0 0.036 0.98 63.9 106.8
2 1 0.040 0.77 71.1 100.4
3 1 0.046 0.64 70.8 NA
4 4 0.042 0.75 69.9 94.9
5 108 0.043 0.53 79.4 92.3
6 122 0.044 0.69 70.5 90.8
7 135 0.030 0.44 107.5 NA
8 574 0.028 0.60 95.3 140.6
Median (range) 56 (0, 574) 0.041 (0.028, 0.046) 0.67 (0.44, 0.98) 70.9 (63.9, 107.5) 97.6 (90.8, 140.6)