Pharmacology, pharmacokinetics and safety of recombinant human erythropoietin (rhEPO)


Hematocrit, blood hemoglobin concentration and red cell mass are regulated by the glycoprotein hormone erythropoietin (EPO). The degree of tissue oxygenation is the primary determinant of the expression of the EPO gene in the kidney. Other production sites contribute little to circulating EPO in humans after birth, albeit the liver is the main site of EPO mRNA expression in fetuses. EPO inhibits the programmed cell death (apoptosis) of the erythrocytic progenitors in the bone marrow, and it stimulates their proliferation and differentiation. Lack of EPO results in normochromic normocytic anemia. The physical power of anemic persons is reduced. Anemia can cause fatigue, pallor, shortness of breath, tachycardia and angina pectoris. In severe cases allogeneic red cell transfusion may be required, although there is no clear threshold hemoglobin concentration for intervention. The decision to transfuse is usually based on clinical symptoms due to hypoxia, and on the patient’s age and comorbidity. The transfusion of allogeneic blood components is associated with the risk of immunologic reactions and of bacterial or viral infection. In addition, repeated red blood cell transfusions lead to iron overload. Therefore, the introduction of recombinant human erythropoietin (rhEPO) as an anti-anemic drug for stimulation of erythropoiesis as a substitute for the endogenous hormone has been a major progress in medicine. This chapter provides information on: (a) the genetic engineering and the structure of established rhEPO preparations and the novel erythropoiesis stimulating protein (NESP), (b) molecular aspects of the action of rhEPO, (c) the pharmacokinetics and safety of rhEPO and NESP and (d) future therapeutic approaches.


Continuous Ambulatory Peritoneal Dialysis Darbepoetin Alfa Recombinant Human Erythropoietin Blood Hemoglobin Concentration rhEPO Treatment 


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© Springer-Verlag/Wien 2002

Authors and Affiliations

  1. 1.Institute of PhysiologyMedical University of LuebeckLuebeckGermany

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