title: Once-monthly administration of darbepoetin alfa for the treatment of patients with chronic heart failure and anemia: a pharmacokinetic and pharmacodynamic investigation.
abstract: In patients with chronic heart failure (CHF), anemia is associated with more severe symptoms and worse prognosis. Erythropoiesis-stimulating proteins (ESPs) increase hemoglobin and may be of therapeutic benefit. We investigated the pharmacokinetics and pharmacodynamics of the long-acting ESP, darbepoetin alfa, administered on 2 occasions 1 month apart to 30 healthy subjects and 33 patients with symptomatic CHF and anemia (hemoglobin<or=12.5 g/dL) in 2 randomized, double-blind, placebo-controlled studies. Subcutaneous (SC) and intravenous administration of 0.75 microg/kg of darbepoetin alfa were compared in a crossover study. The second study compared 2.0, 3.0, and 5.0 microg/kg SC doses with placebo. Darbepoetin alfa (0.75 microg/kg SC) pharmacokinetics were similar in CHF patients and healthy subjects, with a mean (+/-SD) bioavailability of 29 (+/-11)% and 37 (+/-8)%, respectively. In anemic CHF patients, mean (+/-SD) increases in hemoglobin at 4 weeks after the second monthly dose of 2.0, 3.0, and 5.0 microg/kg (SC) of darbepoetin alfa were 2.3 (+/-0.6), 1.4 (+/-1.0), and 2.4 (+/-1.9) g/dL, respectively. Darbepoetin alfa 0.75 microg/kg (SC) given twice, 1 month apart, was insufficient to increase hemoglobin in this study. No severe, drug-related adverse events occurred. Darbepoetin alfa administered once monthly elevates and maintains the hemoglobin concentration in patients with CHF and anemia.
authors.affiliation: Department of Cardiology, University of Hull, Castle Hill Hospital, Kingston upon Hull, UK. j.g.cleland@hull.ac.uk
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.forename: John T
authors.initials: JT
authors.lastname: Sullivan
authors.forename: Stephen
authors.initials: S
authors.lastname: Ball
authors.forename: John D
authors.initials: JD
authors.lastname: Horowitz
authors.forename: Balaji
authors.initials: B
authors.lastname: Agoram
authors.forename: Dylan
authors.initials: D
authors.lastname: Rosser
authors.forename: Wayne
authors.initials: W
authors.lastname: Yates
authors.forename: Lwin
authors.initials: L
authors.lastname: Tin
authors.forename: Paulina
authors.initials: P
authors.lastname: Fuentealba
authors.forename: Paul B J
authors.initials: PB
authors.lastname: Burton
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001682:Biological Availability; D002303:Cardiac Output, Low / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002908:Chronic Disease; D018592:Cross-Over Studies; D000068256:Darbepoetin alfa; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa