Once-monthly administration of darbepoetin alfa for the treatment of patients with chronic heart failure and anemia - A pharmacokinetic and pharmacodynamic investigation
Date
2005
Authors
Cleland, J.
Sullivan, J.
Ball, S.
Horowitz, J.
Agoram, B.
Rosser, D.
Yates, W.
Tin, L.
Fuentealba, P.
Burton, P.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Cardiovascular Pharmacology, 2005; 46(2):155-161
Statement of Responsibility
John G. F. Cleland, John T. Sullivan, Stephen Ball, John D. Horowitz, Balaji Agoram, Dylan Rosser, Wayne Yates, Lwin Tin, Paulina Fuentealba, and Paul B. J. Burton
Conference Name
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.
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Dissertation Note
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© 2005 Lippincott Williams & Wilkins, Inc.