An overview of the pharmacokinetic disposition of darbepoetin alfa.
Darbepoetin alfa is a new erythropoiesis-stimulating protein that has five carbohydrate chains compared with three in recombinant human erythropoietin (r-HuEPO, epoetin alfa). Owing to its increased carbohydrate content, the terminal half-life of darbepoetin alfa is 2-3-fold greater than that of r-HuEPO in patients with chronic kidney disease or cancer. This pharmacokinetic property may allow for less frequent administration of darbepoetin alfa compared with r-HuEPO. Although several regimens are still being tested, a predictable increase was observed in serum concentrations of darbepoetin alfa and no clinically relevant accumulation was seen with once-weekly administration for up to 48 weeks. Preliminary data in patients with cancer suggest that concurrent chemotherapy may influence the pharmacokinetics of darbepoetin alfa. Therefore, the timing of dosing relative to chemotherapy may be important. Darbepoetin alfa, through its potential for less frequent dosing, offers a more convenient treatment option than r-HuEPO for patients with anemia secondary to cancer or kidney disease.
Zamboni
William C
WC
Department of Phamaceutical Services, School of Pharmacy, University of Pittsburgh, Pennsylvania 15213, USA. zamboniwc@msx.upmc.edu
Stewart
Clinton E
CE
D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D002986:Clinical Trials as Topic; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D006397:Hematinics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism; D009369:Neoplasms / Q000150:complications / Q000378:metabolism
D000970:Antineoplastic Agents; D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa