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Pharmacokinetics of erythropoiesis-stimulating agents

  • Sameer Doshi
  • Juan Jose Perez-Ruixo
  • Graham R. Jang
  • Andrew T. Chow
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

Erythropoietin (EPO) is a 30.4 kDa glycoprotein hormone secreted by the kidneys in response to tissue hypoxia, which stimulates red blood cell production. To regulate erythrocyte production, recombinant human EPO (rHuEPO) activates the EPO receptor (EPOR) and stimulates the proliferation and differentiation of erythrocytic progenitors in the bone marrow, leading to reticulocytosis and increased erythrocyte numbers and hemoglobin concentration in the blood. Epoetin alfa, the first commercial form of rHuEPO marketed in the United States of America (USA) and European Union (EU), and epoetin beta marketed outside the USA are both expressed in Chinese hamster ovary (CHO) cells. Both epoetins have a 165-amino acid sequence identical to human urinary EPO, contain three sialic acid-containing N-linked and one O-linked carbohydrate chains [1] leading to the same biologic effects as endogenous EPO [2, 3, 4]. No important differences in clinical efficacy are apparent between epoetin alfa and epoetin beta, and they are generally used interchangeably [5]. Darbepoetin alfa is a hyperglycosylated rHuEPO analog with five amino acid changes and two additional N-linked carbohydrate chains, which has the same mechanism of action as rHuEPO. Darbepoetin alfa, however, has a three-fold increased serum half-life [6, 7, 8], and increased in vivo potency [9], allowing for more convenient modes of administration, including extended dosing intervals [10, 11].

Keywords

Chronic Kidney Disease Subcutaneous Administration Darbepoetin Alfa Recombinant Human Erythropoietin Bone Marrow Ablation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag/Switzerland 2009

Authors and Affiliations

  • Sameer Doshi
    • 1
  • Juan Jose Perez-Ruixo
    • 2
  • Graham R. Jang
    • 1
  • Andrew T. Chow
    • 1
  1. 1.Department of Pharmacokinetics and Drug MetabolismAmgenThousand Oaks
  2. 2.Department of Pharmacokinetics and Drug MetabolismAmgen IncSpain

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