title: Comparison of epoetin alfa and darbepoetin alfa biological activity under different administration schedules in normal mice.
abstract: The unit of erythropoietic activity has long been the standard by which erythropoietic agents are judged, but the development of long-acting agents such as darbepoetin alfa has highlighted the shortcomings of this approach. To this point, we compared the in vivo activity of Epoetin alfa and darbepoetin alfa per microgram of protein core. Using the established mass-to-unit conversion for Epoetin alfa (1 microg congruent with 200 U), we then calculated darbepoetin alfa activity in units. Activity varied with treatment regimen (1 microg darbepoetin alfa congruent with 800 U for 3 times weekly dosing to 8,000 U for a single injection). This analysis reveals the inadequacy of evaluating darbepoetin alfa activity in terms of standard erythropoietic units. We therefore propose that for molecules with heightened biological activity, a more legitimate basis for comparison is the protein mass.
authors.affiliation: Department of Hematology, Amgen, Thousand Oaks, Calif., USA.
authors.forename: Barbra J
authors.initials: BJ
authors.lastname: Sasu
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hartley
authors.forename: Henry
authors.initials: H
authors.lastname: Schultz
authors.forename: Patricia
authors.initials: P
authors.lastname: McElroy
authors.forename: Raheemuddin
authors.initials: R
authors.lastname: Khaja
authors.forename: Steven
authors.initials: S
authors.lastname: Elliott
authors.forename: Joan C
authors.initials: JC
authors.lastname: Egrie
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Browne
authors.forename: C Glenn
authors.initials: CG
authors.lastname: Begley
authors.forename: Graham
authors.initials: G
authors.lastname: Molineux
mesh_terms: D000818:Animals; D000068256:Darbepoetin alfa; D004334:Drug Administration Schedule; D000068817:Epoetin Alfa; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000592:standards; D005260:Female; D051379:Mice; D011994:Recombinant Proteins; D012015:Reference Standards
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa