Erythropoietin

Identification

Name
Erythropoietin
Accession Number
DB00016 / 64FS3BFH5W
Groups
Abseamed
Description

Erythropoietin (EPO) is a increase issue produced within the kidneys that stimulates the manufacturing of red blood cells. it really works via promoting the department and differentiation of dedicated erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was advanced by means of Amgen Inc. in 1983 as the first rhEPO commercialized inside the united states of america, accompanied through different alfa and beta formulations. Epoetin alfa is a one hundred sixty five-amino acid erythropoiesis-stimulating glycoprotein produced in cell subculture the use of recombinant DNA generation and is used for the treatment of patients with anemia associated with numerous scientific conditions, consisting of continual renal failure, antiviral drug remedy, chemotherapy, or a high threat for perioperative blood loss from surgical methods [FDA Label]. It has a molecular weight of approximately 30,four hundred daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product incorporates the equal amino acid collection of isolated herbal erythropoietin and has the identical organic pastime as the endogenous erythropoietin. Epoetin alfa biosimilar, which includes Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to permit extra get admission to to remedy options for patients inside the market [L2784]. The biosimilar is accredited through the FDA and EMA as a secure, powerful and low priced organic product and presentations equal medical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously.

Pharmacology

Pharmacodynamics

Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label].

Indication

Indicated in adult and paediatric patients for the: - treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis. - treatment of anemia due to zidovudine in patients with HIV-infection. - treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy. - reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery.

Action

Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ∼100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C-γ1 [A33079].