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.
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 mg/kg) of darbepoetin to 10 neonates who had a hemoglobin p10.5 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/ml 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 mg/kg administered SC. Journal of Perinatology (2006) IntroductionThe darbepoetin molecule was created by biologically modifying recombinant erythropoietin (rEpo) in order to generate five carbohydrate-binding sites, compared with three in rEpo. This modification produced a more potent erythropoietic stimulator with the advantage of requiring less frequent dosing.
Objective: Previous studies suggest that darbepoetin might stimulate erythropoiesis in preterm neonates more effectively if injected subcutaneously (s.c.) than if infused intravenously (i.v.). It has been postulated that this is because very high plasma concentrations after i.v. dosing result in urinary loss of the drug. However, this theory has not been tested systematically, and no direct comparisons have been made between s.c. and i.v. dosing of darbepoetin in preterm neonates.Study design: Preterm neonates were eligible for this pilot study if they were born at p32 weeks gestation with a weight of p1500 g, and had a hemoglobin p10.5 g/dl. The darbepoetin was given (4 mg/kg) i.v., over 4 h, if an i.v. was already in place and s.c. if no i.v. was in place. Urine was collected for drug quantification before dosing and for 48 h after. Blood was obtained for immature reticulocyte fraction (IRF), absolute reticulocyte count (ARC) and reticulocyte % before and 96 h after dosing.
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