Darbepoetin administration to neonates undergoing cooling for encephalopathy: a safety and pharmacokinetic trial

Pediatr Res. 2015 Sep;78(3):315-22. doi: 10.1038/pr.2015.101. Epub 2015 May 21.


Background: Despite therapeutic hypothermia, neonates with encephalopathy (NE) have high rates of death or disability. Darbepoetin alfa (Darbe) has comparable biological activity to erythropoietin, but has extended circulating half-life (t(1/2)). Our aim was to determine Darbe safety and pharmacokinetics as adjunctive therapy to hypothermia.

Study design: Thirty infants (n = 10/arm) ≥36 wk gestation undergoing therapeutic hypothermia for NE were randomized to receive placebo, Darbe low dose (2 μg/kg), or high dose (10 μg/kg) given intravenously within 12 h of birth (first dose/hypothermia condition) and at 7 d (second dose/normothermia condition). Adverse events were documented for 1 mo. Serum samples were obtained to characterize Darbe pharmacokinetics.

Results: Adverse events (hypotension, altered liver and renal function, seizures, and death) were similar to placebo and historical controls. Following the first Darbe dose at 2 and 10 μg/kg, t(1/2) was 24 and 32 h, and the area under the curve (AUC(inf)) was 26,555 and 180,886 h*mU/ml*, respectively. In addition, clearance was not significantly different between the doses (0.05 and 0.04 l/h). At 7 d, t(1/2) was 26 and 35 h, and AUC(inf) was 10,790 and 56,233 h*mU/ml*, respectively (*P < 0.01).

Conclusion: Darbe combined with hypothermia has similar safety profile to placebo with pharmacokinetics sufficient for weekly administration.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Area Under Curve
  • Brain Diseases / drug therapy*
  • Darbepoetin alfa / pharmacokinetics*
  • Darbepoetin alfa / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Erythropoietin / therapeutic use
  • Female
  • Humans
  • Hypothermia / drug therapy
  • Hypothermia, Induced*
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Male
  • Young Adult


  • Erythropoietin
  • Darbepoetin alfa