Format

Send to

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

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

Author information

1
Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
2
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
3
1] Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah [2] Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
4
Division of Neonatology, Department of Pediatrics, Vanderbilt University, Nashville, Tennessee.
5
Division of Neonatology, Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico.
6
Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, Washington.
7
Intermountain Healthcare, McKay Dee Hospital, Ogden, Utah.

Abstract

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.

PMID:
25996892
PMCID:
PMC5564328
DOI:
10.1038/pr.2015.101
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center