Abstract
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 ⩽32 weeks gestation with a weight of ⩽1500 g, and had a hemoglobin ⩽10.5 g/dl. The darbepoetin was given (4 μg/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.
Results:
Ten preterm neonates were studied: five received i.v. and five received s.c. darbepoetin. No adverse effects of the administrations were detected. IRF, ARC and reticulocyte % increased in the i.v. and s.c. recipients, and no difference in magnitude of increase was apparent between the groups. Before the darbepoetin was administered, none of the patients had any erythropoietin (Epo) detected in their urine. After i.v. dosing, no darbepoetin was detected in any of the samples, on any of the subjects, over the subsequent 48 h. After s.c. dosing, three of the patients had minimal urinary Epo detected. The patient with the largest urinary loss of drug had only 0.13% of the administered dose detected in the urine. Thus, essentially no urinary loss of drug was observed following either i.v. or s.c. darbepoetin dosing.
Conclusion:
Darbepoetin loss into the urine was below detectable limits among seven patients, while three had minimally detectable urinary losses. i.v. and s.c. dosing resulted in approximately equivalent increases in reticulocyte response when measured 96 h after dosing. On this basis, we speculate that if a patient who is to receive darbepoetin has an i.v. in place, the drug can be given i.v., thus avoiding any discomfort associated with an s.c. injection.
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Acknowledgements
We thank the NICU nurses at the McKay-Dee NICU for their valuable assistance with this study.
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Warwood, T., Ohls, R., Lambert, D. et al. Urinary excretion of darbepoetin after intravenous vs subcutaneous administration to preterm neonates. J Perinatol 26, 636–639 (2006). https://doi.org/10.1038/sj.jp.7211596
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DOI: https://doi.org/10.1038/sj.jp.7211596
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