Darbepoetin alfa is more potent in vivo and can be administered less frequently than rHuEPO

Abstract

To date, human studies in a dialysis population have confirmed the pharmacokinetic differences in half life and clearance between NESP and r- HuEPO (Macdougall, 1999). However, studies in humans using NESP have shown an efficacy profile that is comparable to r-HuEPO (Coyne et al, 2000; Nissenson et al, 2000; Locatelli et al, 2001). These studies reinforce the fact that results garnered from animal models are not necessarily indicative of what is to be ascertained in humans. REFERENCES

Erythropoietins: A common mechanism of action

“…Early attempts to improve rhEPO included enhancing molecular stability or increasing affinity for EPOR [73]. However, increased affinity did not necessarily increase in vivo biological potency, because serum t 1/2 was the primary driver of the degree of response [9,28,74]. The exception was modifications that yielded molecules with an affinity that was too low, resulting in ineffective EPOR dimerization and activation.…”

“…Both endogenous and recombinant EPO have microheterogeneity in carbohydrate structures with variation in sialic acid contentdup to 14 attached sialic acid residues [74,[80][81][82]. The importance of sialic acid content for clearance was noted in experiments with rhEPO isoforms, revealing a direct and positive relationship between sialic acid content and in vivo potency [74].…”

“…Both endogenous and recombinant EPO have microheterogeneity in carbohydrate structures with variation in sialic acid contentdup to 14 attached sialic acid residues [74,[80][81][82]. The importance of sialic acid content for clearance was noted in experiments with rhEPO isoforms, revealing a direct and positive relationship between sialic acid content and in vivo potency [74]. The molecules with increased sialic acid content had reduced affinity for the EPOR and increased serum t 1/2 , suggesting that a longer t 1/2 was a stronger determinant of potency than was receptor affinity.…”

Erythropoiesis‐stimulating agents and other methods to enhance oxygen transport

“…Lasne and colleagues combined diafiltration with IEF and double immunoblotting ( Lasne et al ., 2002 ; Lasne, 2003 ) and demonstrated that rHuEpo had a different ‘fingerprint’ with more basic isoforms compared with urinary eEpo ( Lasne and De Ceaurriz, 2000 ). Some differential clearance of the most basic isoforms of rHuEpo ( Egrie and Browne, 2002a ) resulted in an enrichment of the more acidic species over time ( Catlin et al ., 2002 ; Lasne et al ., 2002 , 2007a ; Breidbach et al ., 2003 ); however, the pattern of administered rHuEpo compared with rHuEpo excreted in urine was not substantially altered. Thus, when used appropriately, the test can detect doping with rHuEpo.…”

Managing Anemia in the Critically Ill Patient

“…These products differ in their biochemical structure, pharmacokinetic profile, and receptor-binding affinity. 65,66 The amino acid sequence of epoetin alfa, produced with recombinant DNA technology, is identical to that of endogenous erythropoietin. In contrast, darbepoetin alfa differs from the endogenous human protein in several respects, including five amino acid mutations and a higher molecular weight, which is due, in part, to increased carbohydrate content (~52% carbohydrate for darbepoetin alfa vs ~40% carbohydrate for epoetin alfa).…”