Pharmacokinetics of Novel Erythropoiesis Stimulating Protein Compared with Epoetin Alfa in Dialysis Patients
| Autor: | Joan C. Egrie, Stephen J. Gray, Iain C. Macdougall, Orlaith Elston, Barbara Jenkins, Cormac P. Breen, J K Browne |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Male medicine.medical_specialty Methoxy polyethylene glycol-epoetin beta Darbepoetin alfa Subcutaneous injection Double-Blind Method Pharmacokinetics Internal medicine Humans Medicine Erythropoiesis Erythropoietin Aged Volume of distribution Cross-Over Studies business.industry Epoetin alfa General Medicine Middle Aged Recombinant Proteins Continuous erythropoietin receptor activator Endocrinology Nephrology Female business Half-Life medicine.drug |
| Zdroj: | Journal of the American Society of Nephrology. 10:2392-2395 |
| ISSN: | 1046-6673 |
| DOI: | 10.1681/asn.v10112392 |
| Popis: | Novel erythropoiesis stimulating protein (NESP) is a hyperglycosylated analogue of recombinant human erythropoietin (Epoetin) which has an increased terminal half-life in animal models. The aim of this study was to extend these observations to humans. Using a double-blind, randomized, cross-over design, the single-dose pharmacokinetics of Epoetin alfa (100 U/kg) and an equivalent peptide mass of NESP were compared following intravenous bolus in 11 stable peritoneal dialysis patients. This was followed by an open-label study to determine the single-dose pharmacokinetics of an equivalent peptide mass of NESP by subcutaneous injection in six of these patients. The mean terminal half-life for intravenous NESP was threefold longer than for intravenous Epoetin (25.3 versus 8.5 h), a difference of 16.8 h (95% confidence interval, 9.4 to 24.2 h, P = 0.0008). The area under the serum concentration-time curve was significantly greater for NESP (291.0 +/- 7.6 ng x h per ml versus 131.9 +/- 8.3 ng x h per ml; mean +/- SEM; P < 0.0005), and clearance was significantly lower (1.6 +/- 0.3 ml/h per kg versus 4.0 +/- 0.3 ml/h per kg; mean +/- SEM; P < 0.0005). The volume of distribution was similar for NESP and Epoetin (52.4 +/- 2.0 ml/kg versus 48.7 +/-2.1 ml/kg; mean +/-SEM). The mean terminal half-life for subcutaneous NESP was 48.8 h. The peak concentration of subcutaneous NESP was approximately 10% of that following intravenous administration, and bioavailability was approximately 37% by the subcutaneous route. The longer half-life of NESP is likely to confer a clinical advantage over Epoetin by allowing less frequent dosing in patients treated for anemia. |
| Databáze: | OpenAIRE |
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