Human erythropoietin recombinant

Erythropoietin is a growth factor produced by interstitial cells of the kidney in response to hypoxia. Erythropoietin stimulates haematopoiesis in the bone marrow. Recombinant human erythropoietin is used to treat anemias, e.g. anemia caused by chronic renal failure and anemia in AIDS and cancer patients. 

Tran, A. D., Park, S., Lisi, P. J., Huynh, O. T., Ryall, R. R., and Lane, P. A., Separation of carbohydrate-mediated microheterogeneity of recombinant human erythropoietin by free solution capillary electrophoresis. Effects of pH, buffer type and organic additives,. Ckromatogr., 542, 459, 1991. 

Studies have shown that in patients with chemotherapy-related anemia, therapy with erythropoietin products (epoetin-alfa and darbepoetin) can increase hemoglobin, decrease transfusion requirements, and improve quality of life.12 Epoetin is recombinant human erythropoietin, and darbepoetin is structurally similar to endogenous erythropoietin. Both bind to the same receptor to stimulate red blood cell production. Darbepoetin differs from epoetin in that it is a glycosylated form and exhibits a longer half-life in the body. The half-lives of a single subcutaneous injection of epoetin or darbepoetin in patients are roughly 27 and 43 hours, respectively. 

Yuen, C.T., Stoning, P.L., Tiplady, R.J. et al. (2003) Relationships between the A-glycan structures and biological activities of recombinant human erythropoietins produced using different culture conditions and purification procedures. British Journal of Haematology, 121 (3), 511-526. 

Buemi, M., Aloisi, C., Cavallaro, E., Corica, F., Floccari, F., Grasso, G., Lasco, A., Pettinato, G, Ruello, A., Sturiale, A., and Frisina, N. 2002. Recombinant human erythropoietin more than just the correction of uremic anemia. Journal of Nephrology 15(2), 97-103. 

Engert, A. 2005. Recombinant human erythropoietin in oncology current status and further developments. Annals of Oncology 16(10), 1584-1595. 

Heuser, M. and Ganser, A. 2006. Recombinant human erythropoietin in the treatment of nonrenal anemia. Annals of Hematology 85(2), 69-78. 

Strauss, R. 2006. Controversies in the management of the anemia of prematurity using single-donor red blood cell transfusions and/or recombinant human erythropoietin. Transfusion Medicine Review 20(1), 34-44. 

Boss H J., Watson D.B., and Rush R.S. (1998), Peptide capillary zone electrophoresis mass spectrometry of recombinant human erythropoietin an evaluation of the analytical method, Electrophoresis 19(15), 2654—2664. 

Ghobrial, I.A., D.T. Wong, and B.G. Sharma (1997). An immuno-ligand assay for the detection and quantitation of contaminating proteins in recombinant human erythropoietin (r-HuEPO). BioPharm-Technol Bus 10(1) 42 45. 

Varlet-Marie, E., Gaudard, A., Audran, M., Gomeni, R., and Bressolle, F., Pharmacokinetic-pharmacodynamic modeling of recombinant human erythropoietin in athletes, Int. J. Sports Med., 24,2S2-2S7,2003. 

Bietlot, H. P., and Girard, M. (1997). Analysis of recombinant human erythropoietin in drug formulations by high-performance capillary electrophoresis. /. Chromatogr. A 759, 177—184. 

Zhou, G. H., Luo, G. A., Zhou, Y, Zhou, K. Y, Zhang, X. D., and Huang, L. Q. (1998). Application of capillary electrophoresis, liquid chromatography, electrospray mass spectrometry and matrix-assisted laser desorption/ionization time of flight mass spectrometry to the characterization of recombinant human erythropoietin. Electrophoresis 19, 2348—2355. 

Weise A, Altmann F, Rodriguez-Franco M, Sjoberg ER, Baumer W, Launhardt H, Kietzmann M, Gorr G. (2007) High-level expression of secreted complex glycosylated recombinant human erythropoietin in the Physcomitrella D-fuc-t D-xyl-t mutant. Plant Biotechnol J 5 389 01. 

Epoetin Alfa [Erythropoietin/ EPO] (Epogen/ Procrit) [Recombinant Human Erythropoietin] WARNING Use lowest dose possible may be associated w/1 CV, thromboembolic events /or mortality D/C if Hgb >12 g/dL Uses CRF associated anemia zidovudine Rx in HIV-infected pts, CA chemo -1- transfusions associated w/ surgery Action Induces ery-thropoiesis Dose Adul Peds. 50-150 Units/kg IV/SQ 3x/wk adjust dose q4-6wk PRN Surgery 300 Units/kg/d x 10 d before to 4 d after -I dose if Hct 36% or Hgb, T > 12 g/dL or Hgb t >1 g/dL in 2-wk pmod hold dose if Hgb >12 g/dL Caution [C, +] Contra Uncontrolled HTN Disp Inj SE HTN, HA, fatigue, fever, tach, NA Interactions None noted EMS Monitor ECG for hypokalemia (peaked T waves) t risk of CV thrombotic events OD May cause HA, dizziness, SOB and polycythemia symptomatic and supportive... 

Buemi, M. et al. (2002). Recombinant human erythropoietin more than just the correction of uremic anemia. J. Nephrol. 15(2), 97-103. 

Spivak, J. (1994). Recombinant human erythropoietin and the anaemia of cancer. Blood 84(4), 997-1004. 

Recombinant human erythropoietin for intravenous or subcutaneous injection is available as epoetin alfa, epoetin beta and since 2001 as darbe-poeitin alfa. Epoetin alfa and epoetin beta have different carbohydrate moieties. When administered intravenously the elimination half-life of epoetin alfa is approximately 10 hours. Subcutaneous bioavailability is 20-50% of IV and peak concentrations are achieved after some 20 hours. The recommended initial dose is 50-100 units/kg three times a week in patients with chronic renal failure. 

Recombinant human erythropoietin is available. It is given by parenteral route (IV or SC). 

An inverse log-linear relationship has been found between hematocrit and plasma erythropoietin in anemic patients with normal renal function. Patients with chronic renal failure have inappropriately low erythropoietin levels for their degree of anemia [10]. The severity of anemia correlates with the extent of renal dysfunction. Intravenous or subcutaneous recombinant human erythropoietin given three times a week is the treatment of choice. Some patients seem to do well on only one injection per week. One version of erythropoietin, Epocrit, marketed outside the United States, has been associated with pure red cell aplasia. 

Abbreviations rhuEPO, recombinant human erythropoietin NESP, novel erythropoiesis stimulating protein derived from genetic modification of rhuEPO to create two additional N-linked gylcosylation sites. 

Anabolic steroids are also still used in refractory anemias, although with recombinant human erythropoietin now widely available they appear to be seen mainly as a means of increasing the response to erythropoietin in highly resistant cases combination treatment with erythropoietin, a glucocorticoid, and nandrolone has also been recommended for treating myelodysplastic syndromes (13). Again, in such exceptional situations the risks of anabolic steroids have to be accepted. 

Tsiara SN, Chaidos A, Gouva M, Christou L, Panteli K, Kapsali E, Bourantas KL. Successful treatment of refractory anemia with a combination regimen containing recombinant human erythropoietin, low-dose methylpred-nisolone and nandrolone. J Exp Clin Cancer Res 2004 23 47-52. 

Erythropoietin, a 34-39 kDA glycoprotein, was the first human hematopoietic growth factor to be isolated. It was originally purified from the urine of patients with severe anemia. Recombinant human erythropoietin (rHuEpo, epoetin alfa) is produced in a mammalian cell expression system... 

M.C. Wacholtz, N. Minton, and W.J. Jusko. 2004. Pharmacokinetic and pharmacodynamic modeling of recombinant human erythropoietin after single and multiple doses in healthy volunteers. 

Epoetin-oc (recombinant human erythropoietin) is approved for the treatment of anemia in hemodialysis patients and those receiving chemotherapy. A hyperglyco-sylated analogue of erythropoietin (darbepoetin-oc) that has a lower clearance rate and can be dosed less frequently has also been approved. Erythropoietin stimulates the proliferation of erythrocyte progenitor cells in bone marrow and increases peripheral red blood cell (RBC) counts. 

Recombinant human erythropoietin (rHuEpo) may increase the risk of thrombosis (201). It has been reported that patients with carcinoma of the cervix who received chemotherapy and rHuEpo have an increased risk of symptomatic venous thrombosis (201). In clinical trials where the maintenance hematocrit was 3% on PROCRIT clotting of the arteriovenous shunts occurred at an annual rate of about 0.25 events per patient per year. However, other thrombotic conditions such as cerebrovascular events, transient ischemic attacks, myocardial infarction, or pulmonary embolism occurred at a rate of 0,04 events per patient per year (202). In a separate study of I, I I I untreated patients on hemodialysis, clotting of arteriovenous shunts occurred at a rate of 0.5 events per patient per year. In patients with chronic renal failure on hemodialysis who also had congestive heart failure, ischemic heart disease and venous thrombosis were increased in patients who were treated with PROCRIT targeted to a hematocrit level of 42 3% compared to those targeted to 30 3% (202). It has also been reported... 

Capillary electrophoresis of purified rhEPO (recombinant human erythropoietin) protein. From left to right isoform nos 2, 3, 4, 5, 6, 7, and 8 (according to European Pharmacopea). 

Peptide mapping. (A) Peptide mapping of the international standard of rhEPO (recombinant human erythropoietin) (BRP - European Pharmacopea). (B) Peptide mapping of an rhEPO production lot. 

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