Single-Dose Darbepoetin Administration to Anemic Preterm Neonates

Warwood, T L; Ohls, Robin K.; Wiedmeier, Susan E.; Lambert, D K; Jones, Carolyn Okell; Scoffield, S H; Neeraj, Gupta; Veng‐Pedersen, Peter; Christensen, Robert D.

doi:10.1038/sj.jp.7211387

Cited by 49 publications

(26 citation statements)

References 22 publications

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“…to adults, the t 1/2 is considerably shorter; only 25 h. 7 We previously reported that when 4 mg/kg darbepoetin was administered s.c. to neonates, darbepoetin had a t 1/2 of 21.5 h. 3 In the present study, when given i.v. to neonates, the t 1/2 was much shorter, 10.1 h. The longer t 1/2 after s.c. dosing than after i.v.…”

Section: Discussionmentioning

confidence: 81%

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Intravenous administration of darbepoetin to NICU patients

et al. 2006

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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.

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Section: Discussionmentioning

confidence: 81%

“…1,2 We recently reported results of pharmacokinetic and pharmacodynamic studies following a single subcutaneous (s.c.) dose of darbepoetin to premature neonates. 3 Some neonates who might be treated with darbepoetin have a intravenous (i.v.) line in place, and for these patients perhaps i.v.…”

Section: Introductionmentioning

confidence: 99%

Intravenous administration of darbepoetin to NICU patients

et al. 2006

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“…Evaluation of single-dose pharmacokinetics in preterm infants revealed a similar prolonged half-life. 3,4 Recent studies in animals and humans evaluating the non-hematopoietic effects of ESAs suggest a strong potential for neuroprotection via a variety of mechanisms, including oligodendrogenesis, decreased inflammation, decreased oxidative injury,anddecreasedapoptosis. [5][6][7][8][9] Our group previously reported an increased mental developmental index in former extremely low birth weight (ELBW) infants who had serum Epo concentrations .500 mU/mL, 10 and Neubauer et al reported improved developmental outcomes at 8 to 12 years in former Epotreated preterm infants.…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, Darbe provided this effect with weekly dosing. Given its significantly longer half-life, 3,4 Darbe may be the more attractive and practical choice of ESA for preterm infants. There were no differences in hearing or visual impairment, but significant differences in the incidence of CP were noted, in that only infants in the placebo group had CP identified by examiners masked to the treatment group.…”

Section: Discussionmentioning

confidence: 99%

Cognitive Outcomes of Preterm Infants Randomized to Darbepoetin, Erythropoietin, or Placebo

Ohls¹,

Kamath‐Rayne²,

Christensen³

et al. 2014

PEDIATRICS

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“…13,14 On the basis of our pharmacokinetic studies of darbepoetin administration to VLBW neonates, [15][16][17] we hypothesized that when a neonate qualifies for a late RBC transfusion, a single dose of darbepoetin would counteract the transfusion's erythrosuppressive effect. The single-dose concept was derived from our studies, [15][16][17] and that of Freise et al, 18 who calculated that among VLBW neonates, only a modest increase in plasma erythropoietin is needed to effectuate a several-fold increase in erythropoiesis. With this information, we reasoned that the strategy of single-dose darbepoetin administration accompanying a late transfusion might be worth testing as a means of preventing further NICU transfusions.…”

Section: Introductionmentioning

confidence: 99%

Very low birth weight infants qualifying for a ‘late’ erythrocyte transfusion: Does giving darbepoetin along with the transfusion counteract the transfusion's erythropoietic suppression?

et al. 2011

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Objective: Red blood cell (RBC) transfusions can suppress erythropoiesis. On this basis, RBC transfusions administered to very low birth weight (VLBW) neonates potentially render them more likely to qualify for a subsequent transfusion.Study Design: We hypothesized that 'late' (>14 days after birth) RBC transfusions given to VLBW neonates result in a decrease in reticulocyte count persisting for at least 7 to 10 days. We also hypothesized that a single dose of darbepoetin given along with the transfusion would have the opposite effect, increasing the reticulocyte count for at least 7 to 10 days. To test this, we conducted a single-centered randomized trial with 20 VLBW neonates who, according to our transfusion guidelines, qualified for a late transfusion.Result: VLBW infants about to receive a late RBC transfusion were randomized (1:1) to also receive vs not receive (controls) a single subcutaneous dose of darbepoetin (10 mg kg À1 ). Reticulocyte counts diminished significantly in the controls (a drop of 85±62 Â 10 3 ml À1 (mean ± s.d.) at 7 to 10 days), but increased significantly in the darbepoetin recipients (an increase of 177±120 Â 10 3 ml À1 at 7 to 10 days, P<0.0001). At 7 to 10 days after the transfusion, hematocrits of the controls were 8.1±4.9 points above their pre-transfusion values and of the darbepoetin group were 12.4 ± 2.7 points above their pre-transfusion values (P ¼ 0.033). Conclusion:This was a limited-scope, single-centered, randomized trial intended to pilot-test a new concept in neonatal transfusion practice. Namely, we tested whether a late RBC transfusion suppressed reticulocytosis and whether a concomitant single dose of darbepoetin counteracted that suppression. Using the pilot data presented in this study, larger trials can now be designed to address meaningful clinical outcomes such as transfusion avoidance using this approach.

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Single-Dose Darbepoetin Administration to Anemic Preterm Neonates

Cited by 49 publications

References 22 publications

Intravenous administration of darbepoetin to NICU patients

Intravenous administration of darbepoetin to NICU patients

Cognitive Outcomes of Preterm Infants Randomized to Darbepoetin, Erythropoietin, or Placebo

Very low birth weight infants qualifying for a ‘late’ erythrocyte transfusion: Does giving darbepoetin along with the transfusion counteract the transfusion's erythropoietic suppression?

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