title: Pharmacokinetics and pharmacodynamics of darbepoetin alfa and epoetin in patients undergoing dialysis.
abstract: OBJECTIVE
  The aim of this multicenter, randomized, open-label study was to compare the pharmacokinetic and pharmacodynamic profiles of darbepoetin alfa, a new erythropoiesis-stimulating protein, and recombinant human erythropoietin (epoetin) after repeated intravenous dosing in patients with chronic kidney disease receiving hemodialysis.
  
  
  METHODS
  Forty-seven patients were randomized to receive darbepoetin alfa administered once weekly (n = 17) or 3 times weekly (n = 15) or epoetin administered 3 times weekly (n = 15) for up to 52 weeks. Pharmacokinetic profiles were measured during weeks 1 and 12 and at hemoglobin steady state (defined as a hemoglobin concentration within the target range for 4 consecutive weeks after week 12 with no change in study drug dose) or between weeks 36 and 40, whichever occurred first.
  
  
  RESULTS
  At each of the 3 time points evaluated, the terminal half-life of darbepoetin alfa was 2 to 3 times longer and the clearance approximately 4 times slower than those of epoetin. At week 12, the terminal half-life was 23.4 hours with darbepoetin alfa once weekly, 18.3 hours with darbepoetin alfa 3 times weekly, and 8.0 hours with epoetin 3 times weekly. The pharmacokinetics of darbepoetin alfa was not dependent on dose or time. Mean hemoglobin values at steady state were all approximately 11 g/dL, within the target range of 9.0 to 13.0 g/dL. Safety analyses revealed no differences between darbepoetin alfa and epoetin.
  
  
  CONCLUSIONS
  The pharmacokinetic and pharmacodynamic profiles and safety data for darbepoetin alfa demonstrate that it can be administered less frequently than epoetin in patients with chronic kidney disease receiving hemodialysis, thus simplifying anemia management.
authors.affiliation: University of Alabama at Birmingham, 35294, USA. mallon@nrtc.uab.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Allon
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kleinman
authors.forename: Michael
authors.initials: M
authors.lastname: Walczyk
authors.forename: Charles
authors.initials: C
authors.lastname: Kaupke
authors.forename: Louise
authors.initials: L
authors.lastname: Messer-Mann
authors.forename: Kurt
authors.initials: K
authors.lastname: Olson
authors.forename: Anne C
authors.initials: AC
authors.lastname: Heatherington
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Maroni
mesh_terms: D000328:Adult; D000368:Aged; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011994:Recombinant Proteins; D006435:Renal Dialysis
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa