Comparison of epoetin alfa and darbepoetin alfa biological activity under different administration schedules in normal mice.
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.
Sasu
Barbra J
BJ
Department of Hematology, Amgen, Thousand Oaks, Calif., USA.
Hartley
Cynthia
C
Schultz
Henry
H
McElroy
Patricia
P
Khaja
Raheemuddin
R
Elliott
Steven
S
Egrie
Joan C
JC
Browne
Jeffrey K
JK
Begley
C Glenn
CG
Molineux
Graham
G
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
D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa