Erythropoietin description

A. General description Erythropoietin is a glycoprotein normally produced in the kidneys and is responsible for the stimulation of red blood cell production. Epoetin alfa is derived via recombinant DNA techniques by mammalian cells after the insertion of the human erythropoietin gene its amino-acid sequence is identical to that of endogenous erythropoietin. Epoetin alfa... 

In this case study a simulation strategy, based on a mechanistic PK/PD model, was developed to predict the outcome of the first time in man (FTIM) and proof of concept (POC) study of a new erythropoietin receptor agonist (ERA). A description of the erythropoiesis model, along with the procedures to scale the pharmacokinetics and pharmacodynamics based on preclinical in vivo and in vitro information is presented. The Phase I study design is described and finally the model-based predictions are shown and discussed. 

The half lives of hormones differ with some having very short half lives of less than a few minutes e.g. ACTH, epinephrine and nor-epinephrine, with other hormones e.g., erythropoietin having half lives of about 2-3 h in the mouse and 8-lOh in the dog. (see Woodman,1997 and Reimers,1999 for detailed descriptions of animal hormone structures and properties). The binding of circulating T3 and T4 to plasma proteins differs, and for the hormones that are bound to plasma proteins, any factors affecting protein synthesis and the ratio of freedotal hormone levels must be considered when interpreting data. 

Haematological There have been further descriptions, in case reports and studies [82, 83 84 85 -], of anaemia managed with erythropoietin, blood transfusion or discontinuation of treatment. 

Extraction of crude erythropoietin from serum of phenyl hydrazine anemic rabbits, methanol fractioning of serum, isolation of pseudoglobulins from methanolic fraction II and chromatography of pseudoglobulins on DEAE cellulose, were performed according to our previous descriptions (1,2,3). 

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