Darbepoetin administration to neonates undergoing cooling for encephalopathy: a safety and pharmacokinetic trial.
Pediatr Res
; 78(3): 315-22, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-25996892
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. STUDYDESIGN:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encefalopatias
/
Darbepoetina alfa
/
Hipotermia Induzida
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article