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 hemoglobinand 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 CHFand anemia ( hemoglobin≤12.5 g/dL) in 2 randomized, double-blind, placebo-controlled studies. Subcutaneous (SC) and intravenous administration of 0.75 μg/kg of darbepoetin alfawere compared in a crossover study. The second study compared 2.0, 3.0, and 5.0 μg/kg SC doses with placebo. Darbepoetin alfa(0.75 μg/kg SC) pharmacokinetics were similar in CHFpatients and healthy subjects, with a mean (±SD) bioavailability of 29 (±11)% and 37 (±8)%, respectively. In anemic CHFpatients, mean (±SD) increases in hemoglobinat 4 weeks after the second monthly dose of 2.0, 3.0, and 5.0 μg/kg (SC) of darbepoetin alfawere 2.3 (±0.6), 1.4 (±1.0), and 2.4 (±1.9) g/dL, respectively. Darbepoetin alfa0.75 μg/kg (SC) given twice, 1 month apart, was insufficient to increase hemoglobinin this study. No severe, drug-related adverse events occurred. Darbepoetin alfaadministered once monthly elevates and maintains the hemoglobinconcentration in patients with CHFand anemia.