Objective: Darbepoetin 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 design: We 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.
Results: The 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).
Conclusions: Darbepoetin 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.