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OBJECTIVE Management of anemia of chronic kidney disease (CKD) often includes subcutaneous or intravenous administration of erythropoietin-stimulating agents (ESAs). Mircera, a pegylated continuous erythropoietin receptor agonist, has a longer duration of action and requires less frequent administration than other ESAs. Pediatric experience with Mircera is limited. We retrospectively reviewed our long-term experience of Mircera in a national pediatric nephrology center. METHODS Patients were identified via an electronic patient record database. Data collected included demographics (sex, age, etiology of CKD, CKD stage, dialysis modality), dosing information, and laboratory data--hemoglobin (Hb), parathormone (PTH), ferritin, hematinics prior to commencing Mircera and all subsequent values associated with dose adjustments. RESULTS Seventy-seven patients aged 2 to 18 years, with CKD stages 2 to 5T had received at least 1 dose of Mircera, with 75 patients having sufficient data and a total of 1473 doses. No patients discontinued Mircera owing to adverse effects. One patient experienced a potential severe adverse drug reaction. Mircera was effective in improving or maintaining Hb =10.0 g/dL in most (58/75, 77.3%) patients. The median dose to achieve Hb =10.0 g/dL was 2.1 µg/kg/4 wk. Most doses (1039, 71.5%) were administered 4-weekly. The doses (161, 11.1%) that were administered 6-weekly remained efficacious. Thirty-two patients started Mircera with Hb <10.0 g/dL; 26 (81%) achieved Hb =10.0 g/dL within a median time of 4 months. Mircera was less effective if given every 8 weeks, or in the presence of hyperparathyroidism or hyperferritinemia. CONCLUSION Mircera appears safe and effective in pediatric patients with CKD. [ABSTRACT FROM AUTHOR]

A conjugate of erythropoietin β with 30 kDa linear methoxy poly(ethylene glycol) characterized by the presence of an azo spacer between the protein fragment and poly(ethylene glycol) was developed for import-substitution of Mircera drug in the Russian Federation. The erythropoietic activity of the synthesized conjugate was determined. Its pharmacokinetics in CBA mice were found to be comparable to those of Mircera. The bioequivalence of the proposed azo conjugate and Mircera was established based on the calculated drug pharmacokinetic parameters in mice. [ABSTRACT FROM AUTHOR]

Objective: Besides its hematopoietic function, erythropoietin (EPO) may protect tissues from degenerative disorders. As such, EPO and its receptors were revealed in nonhematopoietic cells, including stromal and endometrial epithelial cells. However, the role of EPO in endometrial disorders is still unknown. Here, we aimed to examine the role of EPO and its receptor activation in the development of endometriosis in rats. Material and Methods: Animals were treated with EPO, darbepoietin (the synthetic form of EPO) or EPO's receptor activator, methoxy polyethylene glycol-epoetin beta (MIRCERA), after development of endometriosis. Endometriosis was induced by estrogen-administration following surgical attachment of endometrial surface on the inner abdominal wall. Treatments were started 3 weeks after induction of endometriosis and continued for the following 3 weeks. For the analysis of recurrence of endometriosis, additional analyses were conducted 3 weeks after cessation of treatments. Results: As compared with vehicle-treated animals, lesion size was reduced significantly and recurrence of endometriosis was not observed in all treatment groups. Histopathologic examination revealed that EPO and darbepoietin were more effective than MIRCERA- and vehicle-treated animals. Conclusion: Here we provide evidence that EPO is a promising candidate for the treatment of endometriosis. Our histopathologic results in particular indicate that EPO is more effective than its receptor activator MIRCERA in the development endometriosis. [ABSTRACT FROM AUTHOR]

The recombinant human erythropoietins epoetin alfa (Eprex®), darbepoetin (Aranesp®) and methoxy polyethylene glycol-epoetin beta (Mircera®) were administered to greyhounds for 7, 10 and 14 days respectively. Blood and urine samples were collected and analysed for erythropoietin by ELISA, LC-MS/MS and western blotting. Limits of confirmation in plasma for western blotting and LC-MS/MS methods ranged from a low of 2.5mIU/mL, and closely matched the sensitivity of ELISA screening. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The detection of doping with MIRCERA (the brand name for Continuous Erythropoietin Receptor Activator, or CERA) is hampered by the limited excretion of the rather large molecule (approximately 60 kDa) in urine. Blood (serum, plasma) in combination with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) appears to be the ideal matrix for detecting all forms of doping with erythropoiesis-stimulating agents (ESAs) because the apparent molecular masses of ESAs are different from the mass of human serum erythropoietin (shEPO). While SDS-PAGE has proven the most sensitive method for the detection of doping with Dynepo, the sensitivity of SDS-PAGE for MIRCERA is drastically decreased. By exchanging the SDS for SARCOSYL (SAR) in the sample and running buffers the sensitivity problem was solved. SARCOSYL, a methyl glycine-based anionic surfactant, is only binding to the protein-part of MIRCERA but not to its polyethylene glycol (PEG)-chain, while SDS binds to both parts. In consequence, the monoclonal anti-EPO antibody (clone AE7A5) no longer interacts with the fully SDS-solubilized MIRCERA molecules. Only those molecules that contain SDS bound to the protein-chain are detected. Due to the inability of SARCOSYL to solubilize PEG-molecules, MIRCERA can be detected on SARCOSYL-PAGE with the same sensitivity as non-PEGylated epoetins. In a typical SAR-PAGE experiment, 200 µL of serum are used, which allows the direct detection of MIRCERA, recombinant epoetins (such as NeoRecormon, Dynepo, NESP), and shEPO in a single experiment and with high (i.e. femtogram) sensitivity. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]