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Pharmacokinetics of erythropoiesis-stimulating agents

  • Chapter
Erythropoietins, Erythropoietic Factors, and Erythropoiesis

Part of the book series: Milestones in Drug Therapy ((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 [2–4]. 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 [6–8], and increased in vivo potency [9], allowing for more convenient modes of administration, including extended dosing intervals [10, 11].

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  1. Department of Pharmacokinetics and Drug Metabolism, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320

    Sameer Doshi, Graham R. Jang & Andrew T. Chow

  2. Department of Pharmacokinetics and Drug Metabolism, Amgen Inc, Spain

    Juan Jose Perez-Ruixo

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  1. Sameer Doshi
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    Steven G. Elliott

  2. MA Foote Associates, Westlake Village, CA, 91362, USA

    Mary Ann Foote

  3. Amgen Inc., One Amgen Center Drive, Mailstop 15-2-A, Thousand Oaks, CA, 91320, USA

    Graham Molineux

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Doshi, S., Perez-Ruixo, J.J., Jang, G.R., Chow, A.T. (2009). Pharmacokinetics of erythropoiesis-stimulating agents. In: Elliott, S.G., Foote, M.A., Molineux, G. (eds) Erythropoietins, Erythropoietic Factors, and Erythropoiesis. Milestones in Drug Therapy. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8698-6_12

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