Actions of Darbepoetin Alfa on Erythropoiesis

Darbepoetin alfa stimulates erythropoiesis by the same mechanisms as those previously discussed for endogenous EPO. In vitro, the affinity of darbepoetin alfa for EPOR is less that that of rHuEPO; however, the increase in mean residence time of darbepoetin alfa results in a prolonged period of time above an erythropoietic threshold (Fig. 3) that more than compensates for the reduced receptor affinity, resulting in increased in vivo activity (56,59).

Erythropoiesis threshhoid

0 12 24 36 48 60 72 84 96 108120132144156168180

Time (hours)

Fig. 3. Darbepoietin alfa has a longer serum half-life than rHuEPO (From ref. 119.)

■—■ rHuEPO i.v. (100 fU/kg) 4—4 Darbepoetin alfa i.v. (0.5 (_ig/kg) A—A Darbepoetin alfa s.c. (0.5 ¡jg/kg)

Erythropoiesis threshhoid

0 12 24 36 48 60 72 84 96 108120132144156168180

Time (hours)

Fig. 3. Darbepoietin alfa has a longer serum half-life than rHuEPO (From ref. 119.)

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