Darbepoetin Alfa
Long-acting erythropoiesis-stimulating glycoprotein with additional sialic acid residues for extended half-life in anemia treatment.
Chemical Identity
| Property | Value |
|---|---|
| Molecular Weight | ~37.1 kDa |
| Amino Acids | 165 (same as EPO) |
| Sialic Acids | Up to 22 (vs 12 for EPO) |
| CAS Number | 209810-58-2 |
| Route | IV, SC |
Structure
Darbepoetin alfa (Aranesp) is a hyperglycosylated analog of erythropoietin with five amino acid substitutions (Asn24, Asn38, Asn83, Thr132, Asn136) creating two additional N-glycosylation sites. The increased sialic acid content (up to 22 residues vs 12 for EPO) extends half-life by reducing renal clearance.
Mechanism of Action
Like EPO, darbepoetin binds EPOR on erythroid progenitors, activating JAK2/STAT5 to promote erythropoiesis. The extended half-life (3x longer than EPO) allows less frequent dosing while maintaining erythropoietic stimulation.
Clinical Applications
- CKD anemia: Every 2-4 week dosing (vs weekly for EPO)
- Chemotherapy-induced anemia: Extended dosing interval
- Anemia of prematurity: Investigational
- Non-inferiority: Comparable efficacy to epoetin at less frequent dosing
Pharmacokinetics
- Half-life: 25.3 hours (IV), 48.8 hours (SC)
- Bioavailability: 37% (SC)
- Peak: 34-58 hours (SC)
- Dosing: Every 1-4 weeks depending on indication
- Route: IV, SC
Safety and Side Effects
Hypertension, headache, arthralgias, nausea, edema, and pure red cell aplasia (rare, antibody-mediated). Target Hgb should not exceed 12 g/dL. Increased cardiovascular events with high hemoglobin targets.
References
- Locatelli, F., et al. (1999). Darbepoetin alfa for CKD anemia. New England Journal of Medicine, 341, 1025-1030.
- Macdougall, I.C. (2002). Darbepoetin alfa: a new therapeutic option for renal anemia. Kidney International, 61, S58-S63.
Test Your Knowledge
Reinforce what you learned about Darbepoetin Alfa with interactive quizzes on Wikipept.
Take a Quiz on Wikipept