Intravenous administration of darbepoetin to NICU patients.

objectiveDarbepoetin can be administered either intravenously (i.v.) or subcutaneously (s.c.). However, no information is available regarding pharmacokinetics and pharmacodynamics following its i.v. administration to neonates. STUDY

designWe administered a single i.v. dose (4 microg/kg) of darbepoetin to 10 neonates who had a hemoglobin < or =10.5 g/dl. Blood was obtained for immature reticulocyte fraction (IRF) and absolute reticulocyte count (ARC), before and 48 h following the dose. Blood was also drawn for pharmacokinetic analysis once before and at four pre-set intervals after dosing.

resultsThe study subjects ranged from 704 to 3025 g (median, 1128 g) birth weight, and were 26.0-40.0 weeks (median, 29.2 weeks) gestation at delivery. When the darbepoetin dose was given, ages ranged from 3 to 28 days (median, 8.5 days) with a hemoglobin of 9.8 +/- 0.7 g/dl (mean +/- s.d.). Doses were administered by i.v. infusion over 4 h. No adverse effects of the infusions were detected. The half-life of darbepoetin (t (1/2)) was 10.1 h (range 9.0-22.7 h), the volume of distribution was 0.77 l/kg (range 0.18-3.05 l/kg) and the clearance was 52.8 ml/h/kg (range 22.4-158.0 ml/h/kg). In the preterm neonates, there was no significant correlation between gestational age, or age at darbepoetin administration, and pharmacokinetic parameters. However, in the term and near-term neonates, volume of distribution correlated significantly with both gestational and age at darbepoetin administration (P < 0.05). Forty-eight hours after dosing, the IRFs and ARCs were elevated in six subjects and not in four. Those with predosing reticulocyte counts >200,000/microl did not have an increase in reticulocytes by 48 h (P < 0.05).

conclusionsDarbepoetin administered i.v. to neonates had a shorter t (1/2), a larger volume of distribution and more rapid clearance than reported in children. We observed a significantly shorter t (1/2) and a less consistent rise in IRF and ARC after i.v. dosing than we previously reported following 4 microg/kg administered SC.