Single-Dose Darbepoetin Administration to Anemic Preterm Neonates

Abstract

OBJECTIVE:

Darbepoetin is longer acting and more potent than recombinant erythropoietin (rEpo). In certain situations, preterm neonates might benefit from rEpo, and for such patients darbepoetin would require fewer doses at a lower cost. However, the proper dose and dosing interval have not been established.

STUDY DESIGN:

We performed a prospective trial in two level III Neonatal Intensive Care Units. Patients <32 weeks gestation at birth, with a birth weight (BW) <1500 g, were eligible for participation if they were >21-days-old and had a hemoglobin (Hgb) concentration ≤10.5 g/dl. In all, 12 were to receive a single subcutaneous (s.c.) dose at either 1 or 4 μg/kg. Once before the dose was given, and at two preset intervals after, blood was obtained for immature reticulocyte fraction (IRF) and absolute reticulocyte count (ARC). Once before and at four preset intervals after, blood was obtained for pharmacokinetic studies.

RESULTS:

The 12 subjects had BWs of 1129±245 g (mean±SD), were 29.2±1.2 weeks gestation at delivery, and were 43±12 days old with an Hgb concentration of 9.6±1.0 g/dl when the darbepoetin was given. Six received 1 μg/kg and six 4 μg/kg. The IRF increased (p<0.05) as did the ARC (p<0.05). The increases in IRF were somewhat greater among the 4 μg/kg recipients (P=0.06). The highest recorded concentrations of drug occurred 6 to 12 hours after administration. The combined 6 and 12 hours values were 185±106 mU/ml in the 1 μg/kg group vs 597±238 in the 4 μg/kg group (p<0.002). The t½ was 26 hours (range 10 to 50). The biovailability-normalized clearance was 19 ml/hour/kg (range 5 to 54).

CONCLUSIONS:

A single s.c. dose of darbepoetin given to preterm neonates accelerated effective erythropoiesis. The pharmacodynamic and pharmacokinetic findings suggest that darbepoetin dosing in neonates would require a higher unit dose/kg and a shorter dosing interval than are generally used for anemic adults.