Erythropoietin serum

Decreased red blood cell (RBC) count, hemoglobin (Hgb) and hematocrit (Hct) iron metabolism may also be altered [iron level, total iron binding capacity (TIBC), serum ferritin level, and transferrin saturation (TSAT)]. Erythropoietin levels are not routinely monitored and are generally normal to low. Urine positive for albumin or protein. 

Decreased RBC count, Hgb, and Hct Decreased serum iron level, TIBC, serum ferritin, and TSAT Decreased erythropoietin levels relative to the degree of hypoxia that is present... 

Although EPO deficiency is the primary cause of CKD anemia, iron deficiency is often present, and it is essential to assess and monitor the CKD patient s iron status (NKF-K/DOQI guidelines). Iron stores in patients with CKD should be maintained so that transferrin saturation (TSAT) is greater than 20% and serum ferritin is greater than 100 ng/mL (100 mcg/L or 225 pmol/L). If iron stores are not maintained appropriately, epoetin or darbepoetin will not be effective, and most CKD patients will require iron supplementation. Oral iron therapy can be used, but it is often ineffective, particularly in CKD patients on dialysis. Therefore, intravenous iron therapy is used extensively in these patients. Details of the pharmacology, pharmacokinetics, adverse effects, interactions, dose, and administration of erythropoietin and iron products have been discussed previously. 

To date, three pharmaceutical companies have entered clinical trials with PHD inhibitors for the treatment of anemia with the most advanced being FG-2216. In clinical studies, compound 2 (likely FG-2216) showed a dose- and time-dependent elevation of plasma erythropoietin after oral administration [66]. Healthy volunteers were orally administered various doses of compound 2 and serum erythropoietin (EPO) concentrations were measured at various times. Compound 2 increased serum EPO levels in a dose-dependent manner and, following administration of the 20 mg/kg dose, a 5-fold increase of EPO levels was observed after 12 h. In the same patent application, the effect of 2 on anemic predialysis patients with no previous rh-EPO exposure was also disclosed. Patients were treated with 2 three times/week for 4 weeks (no dose reported) and the hemoglobin levels were assessed on day 42. The patients who received treatment showed a mean increase in hemoglobin of 1.9 g/dL from baseline values, whereas subjects who received placebo showed a mean decrease of 0.35 g/dL from baseline levels. These data suggest for the first time that an oral PHD inhibitor could be effective for the treatment of anemia. 

Zidovudine-treated, HIV-infected patients Available evidence suggests that patients receiving zidovudine with endogenous serum erythropoietin levels greater than 500 milliunits/mL are unlikely to respond to therapy. 

Initial dose - For patients with serum erythropoietin levels 500 milliunits/mL or less who are receiving a dose of zidovudine 4,200 mg/week or less, the recommended starting dose is 100 units/kg as an IV or subcutaneous injection 3 times/week for 8 weeks. 

Cancer patients on chemotherapy Treatment of patients with grossly elevated serum erythropoietin levels (eg, greater than 200 milliunits/mL) is not recommended. Monitor hemoglobin on a weekly basis in patients receiving epoetin alfa therapy until... 

Mammalian cell culture is more technically complex and more expensive than microbial cell fermentation. It is, therefore, usually only used in the manufacture of therapeutic proteins that show extensive and essential post-translational modifications. In practice, this usually refers to glycosylation and the use of animal cell culture would be appropriate where the carbohydrate content and pattern is essential either to the protein s biological activity, stability or serum half-life. Therapeutic proteins falling into this category include erythropoietin (Chapter 6), the gonadotrophins (Chapter 8), some cytokines (Chapters 4-7) and intact monoclonal antibodies (Chapter 10). 

Akpolat T, Gumus T, Bedir A, Adam B. Acute effect of trandolapril on serum erythropoietin in uremic and hypertensive patients. J Nephrol 1998 11 94-7. 

Hopfer SM, Sunderman FW Jr, Reid MC, et al. 1984. Increased immunoreactive erythropoietin in serum and kidney extracts of rats with NijSj-induced erythrocytosis. Res Commun Chem Pathol Pharmacol 43 299-305. 

Center for Biologies Evaluation and Research (CBER). This center is responsible for the regulation and approval of all biological products intended for use in the treatment, prevention, or cure of diseases or injuries to humans. A biological product is any vims, therapeutic serum, toxin, antitoxin, vaccine, blood or blood component or derivative, or analogous product (5). It also includes products produced by biotechnology, such as interferons and erythropoietins. 

These studies demonstrating a protective effect of sialic acid residues on serum glycoproteins provide an explanation for earlier, conflicting observations about the biological effect of, for example, desialylated erythropoietin, which stimulates erythropoiesis only after direct application to bone-marrow cell-cultures, and not after injection into the blood stream.469 In the latter experiment, only the native, sialylated hormone was active. Rapid clearance and inactivation of follicle-stimulating hormone,470 or interferon,471 after treatment with sialidase may be explained by uptake into liver cells. 

Allergic reactions to ESAs have been infrequent. There have been a small number of cases of pure red cell aplasia (PRCA) accompanied by neutralizing antibodies to erythropoietin. PRCA was most commonly seen in dialysis patients treated subcutaneously for a long period with a particular form of epoetin alfa (Eprex with a polysorbate 80 stabilizer rather than human serum albumin) that is not available in the USA. After regulatory agencies required that Eprex be administered intravenously rather than subcutaneously, the rate of ESA-associated PRCA diminished. However, rare cases have still been seen with all ESAs administered subcutaneously for long periods to patients with chronic kidney disease. 

In selected patients, erythropoietin may also be useful for the treatment of anemia due to primary bone marrow disorders and secondary anemias. This includes patients with aplastic anemia and other bone marrow failure states, myeloproliferative and myelodysplastic disorders, multiple myeloma and perhaps other chronic bone marrow malignancies, and the anemias associated with chronic inflammation, AIDS, and cancer. Patients with these disorders who have disproportionately low serum erythropoietin levels for their degree of anemia are most likely to respond to treatment with this growth factor. Patients with endogenous erythropoietin levels of less than 100 IU/L have the best chance of response, though patients with erythropoietin levels between 100 and 500 IU/L respond occasionally. These patients generally require higher erythropoietin doses (150-300 IU/kg three times a week) to achieve a response, and responses are often incomplete. 

M. Taneke, S. Teshima, T. Hanyo, and Y. Hayashi, Rapid and sensitive method for erythropoietin determination in serum, Clin. Chem.,38 1752(1992). 

Antibodies directed against recombinant erythropoietin have been obtained from rabbits immunized with the hormone and Freunds complete adjuvant [64], Two sets of antibodies are present in the serum of rabbits that have been immunized, Fig. (3C). The results of oxidation of the erythropoietin with periodate, Fig. (25A), reaction of the antibodies with lectins of known carbohydrate specificity, Fig. (25B) and inhibition of the antibodies with the structural monosaccharide residues of the hormone, Fig. (26), have established the types of antibodies to be anti-carbohydrate antibodies and the immunodeterminants for these antibodies are oligosaccharides with the following structure N-acetyl neuraminyl a(2->3)... 

Fig. (26). Inhibition of erythropoietin (E), reaction with serum (S) by N-acetyl-neuraminic acid, (SN), and by lactosamine, (SNL).

Lee, G.M., E.J. Kim, N.S. Kim, S.K. Yoon, Y.H. Ahn, and J.Y. Song. 1999. Development of a serum-free medium for the production of erythropoietin by suspension culture of recombinant Chinese hamster ovary cells using a statistical design. JBiotechnol 69 85-93. 

ANGIOTENSIN II RECEPTOR ANTAGONISTS EPOETIN 1 efficacy of angiotensin II receptor antagonists and possible t risk of hyperkalaemia Angiotensin II is believed to sustain the secretion of erythropoietin and to stimulate the bone marrow to produce erythrocytes. Epoetin has a direct contractile effects on vessels Monitor BP at least weekly until stable. Monitor serum potassium every week until stable, then every 3-6 months... 

FIGURE 32.7 Serum erythropoietin (EPO) concentrations as a function of time after SC injection of 100 U/kg of recombinant human erythropoietin in the thigh and abdomen of 11 healthy volunteers. The bold curve represents the median. (Reproduced with permission from Jensen JD et al. Eur J Clin Pharmacol 1994 46 333-7.)... 

The amount of a substance that can enter the brain by the exdacellular pathw ays is small. However, this route may be therapeutically relevant for compounds that have favorable peripheral pharmacokinetics, such as a long serum half-life and a small volume of distribution (Banks, 2004). Therapeutic antibodies and erythropoietin can access the brain by v ay of the extracellular pathways (Banks et al., 2004a Banks et al., 2002 Banks et al., 2005a Kozlowski et al., 1992) and this may underlie their therapeutic benefits (Alafaci et al., 2000 Ehrenreich et al., 2002 Erbyraktar et al., 2003 Morgan et al., 2000 Janus et al., 2000 DeMattos et al., 2002 Farr et al., 2003 Hock et al., 2003). 

Inorganic cobalt is transported in the blood by albumin and transferrin it is taken up by the liver. The serum concentration amounts to 1.9-7.6 mmol/1. An increased value is a sign of liver cell necrosis (e. g. acute hepatitis). Its biological significance is attributed to its position as a central atom in vitamin B12 and its involvement in the release of renin and erythropoietin. 

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