Request PDF on ResearchGate | On Feb 1, , Hugo Donato and others published Tratamiento con eritropoyetina humana recombinante. Se demostró que el tratamiento con eritropoyetina humana recombinante (EPO rHu) en pacientes en diálisis es altamente efectivo en cuanto a la corrección de. Eritropoyetina humana recombinante para la anemia de la insuficiencia renal crónica en pacientes en prediálisis. This is not the most recent version of this.

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Faculty of Pharmacy, University of Belgrade, Serbia. This work was conducted as a part of projects No and funded by the Ministry of Science, Education and Technological Development, Belgrade, Republic of Serbia.

Balkan endemic nephropathy BEN hemodialysis patients require a higher dose of recombinant human erythropoietin for maintaining target hemoglobin level than patients with other kidney diseases. Comparison of the pharmacokinetics of beta-erythropoietin given subcutaneously to hemodialysis patients with BEN or other kidney diseases non-BEN. The predose plasma level of erythropoietin Epo was subtracted from all postdose levels. The relevant pharmacokinetic parameters were calculated after noncompartmental pharmacokinetic analysis using Kinetica software Thermo Scientific, ver.

Although basal plasma Epo concentration was similar in BEN These differences remained significant after adjustment for patient characteristics age, sex, hemodialysis duration, ferritin, PTH and ACEI use. No significant differences between groups were found in maximal Epo concentration, time to maximum Epo concentration, area eritropoyetinx the curve from time of dosing extrapolated to infinity, clearance, mean residence time of Epo between groups both before and after adjustment.

Pharmacokinetic analysis of beta-erythropoietin detected a yumana longer elimination half-life in BEN than in non BEN patients.

This finding needs to be confirmed in a well-controlled eritroppyetina with a larger sample size. Balkan endemic nephropathy, Human recombinant erythropoietin, Pharmacokinetics. El nivel de EPO en recombinwnte previo a la dosis se sustrajo de eritropoyeyina los niveles que se obtuvieron tras administrarla.

Anemia was described as a characteristic of Balkan endemic nephropathy BEN in early reports on the disease, 1,2 so Danilovic 3 included it among reocmbinante criteria for diagnosis.

However, several authors reported no significant differences between anemia in BEN and other kidney diseases. We recently showed that BEN hemodialysis patients required a higher dose of recombinant human erythropoietin for maintaining the target hemoglobin level than patients with other kidney diseases.

However, the influence of ESA pharmacokinetics on hematopoietic response has not been sufficiently investigated. Pharmacokinetics studies were mostly devoted to the pharmacokinetics of diverse ESA administered by different humsna, as well as to the pharmacokinetics of ESA in various groups of chronic kidney disease patients and healthy persons. The aim of this study was to compare the pharmacokinetics of beta-erythropoietin beta-Epo given subcutaneously to BEN patients and patients with other kidney diseases non-BEN and to evaluate the factors influencing beta-Epo kinetics.

The prospective clinical study was performed according to good clinical practice and in accordance with the Declaration of Helsinki in three clinical centers. The Ethics Committee of the Clinical Center of Serbia evaluated and approved the study and the participants gave informed consent.

A total of 24 subjects was selected from the population of hemodialysis patients according to the following inclusion criteria: Among the remaining 96 patients 40 BEN and 56 others who met inclusion criteria, 10 with BEN and 14 with other huamna diseases were selected using systematic sampling i. The group with other kidney diseases consisted of 8 patients with glomerulonephritis, 3 with hypertensive nephropathy, 2 with reflux nephropathy and 1 with polycystic kidney disease.

All patients were treated thrice weekly for h bystandard bicarbonate hemodialysis using polysulphone membrane dialyzers. Serum levels of iron, ferritin, transferrin saturation, C-reactive protein CRPalbumin, urea, creatinine, calcium, rrcombinante and parathyroid hormone PTH were determined in each patient at the time of study. Beta-erythropoietin administration and blood sampling. The dose of beta-Epo was adjusted to attain the erifropoyetina target range defined by European best practice guidelines for the management of anemia in patients with chronic renal failure In addition, iron status was assessed and supplementary iron given according to the same guidelines.


The last beta-Epo dose prior to pharmacokinetics blood samplingwas omitted in egitropoyetina patients but recontinued at the first hemodialysis session after the study with the dose used before. Venous blood was collected into heparinized tubes before and at 2, 6, 8, 12, 24, 48, and 72 only in five patients h after beta-Epo administration.

Blood samples were centrifuged for 10 min and plasma stored frozen until analysis. Erythropoietin Epo concentration was determined in all samples on the same day by chemiluminescent immunoassay for erythropoietin on an Immulite analyzer Siemens Healthcare Diagnostics. For pharmacokinetic analysis the predose plasma recomvinante of Epo was subtracted from all postdose levels of Epo for each patient. Noncompartmental pharmacokinetic analysis using Kinetica software Hymana Scientific, ver.

The results were expressed as mean values with standard deviations. The significance of differences between mean values for groups was calculated using the Mann-Whitney U test and Student’s t-test. Analysis of covariance Bumana was used to adjust these differences for patient characteristics that differed between groups: All analyses were performed using the SPSS ver. The study involved 24 hemodialysis patients, 10 patients with BEN and 14 with other kidney diseases, selected from 96 patients 40 BEN and humzna others who met the inclusion criteria.

Their main characteristics are presented in Table 1. Main characteristics of the patients ACEI: Results of laboratory analyses in the examined individuals are given in Table 2.

Predialysis serum creatinine and PTH concentrations were significantly lower, and serum calcium concentration was significantly higher in the BEN than in the non-BEN group. Basal plasma Recpmbinante concentration in BEN patients ranged eritropoyetinna 7. Results of laboratory analyses in examined patients Recomginante C reactive protein; Epo: After beta-Epo administration plasma Epo slowly increased and Recombiinante max was achieved after The presented profiles show greater inter-individual variability in Epo concentration but a faster decrease of Epo level during the elimination phase in non-BEN than in BEN patients.

The pharmacokinetic parameters of Epo are presented in Table 3. When adjusted these differences remained statistically significant 0. Also, the difference in other pharmacokinetic parameters presented in Table 3 remained insignificant after adjustment. A number of pharmacokinetic studies of ESA have been published, but comparison between them is difficult due to numerous methodological differences.

Recent studies were largely devoted to the pharmacokinetics of new ESAs 10,12,14 and were usually carried out in healthy persons. The present study was initiated from earlier data involving BEN and 94 non-BEN patients, which showed that significantly higher beta-Epo doses for reaching and maintaining target hemoglobin level were necessary in BEN than in non-BEN patients.

A number of factors may contribute to insufficient hematopoietic response to ESAs: In addition, none of the mentioned factors for Epo hyporesponsiveness were significantly more pronounced in BEN than in non-BEN patients, except for older age.

Our patients had iron reserves above the upper limit of normal and a similar proportion of subjects from each group used iron supplements. Similar inter-individual differences were found in time needed to reach Epo C max. The values of C max and t max are comparable to those found by other authors, taking into account the above mentioned differences in methodology.

Eritropoyetina Humana Recombinante Delta –

However, for protein and peptide drugs, dependency on active tissue uptake, binding to intra- and recokbinante proteins can substantially increase the value of Vd.

Therefore, not only the distribution by itself, but also the process of elimination and interaction directly with the Epo receptor on the red blood cell surface play an important role in increasing the values of Vd for Epo in comparison to its physiological distribution limited to extravascular space in the body.


Despite long clinical experience with ESAs, the mechanisms involved in their elimination have not been fully elucidated. It seems most likely that both native Epo and recombinant drugs are degraded following receptor-mediated uptake, mainly in the bone marrow.

In addition, recently described mechanisms independent of the Epo receptor elimination pathway, 29 may also contribute to slower Epo elimination in BEN patients. The main limitation of our study was the small number of patients in each group, and they were not matched in age.

BEN is a slow progressive chronic kidney disease and patients who progress to end-stage renal disease usually start hemodialysis in the seventh decade of life. As the main organs involved in Epo elimination are the kidneys and bone marrow and both kidney function and bone marrow cellularity decrease with age, the authors suggested that age and creatinine influence Epo elimination.

Eritropoyetina Humana Recombinante

Although an impact of age on Epo elimination in our patients cannot be fully excluded, neither age nor other covariates rrcombinante differed between the groups recombinange found affect Epo elimination in the ANCOVA model. On the other hand, residual renal function was maintained longer in BEN patients than in those with other kidney diseases 34 and our Numana patients were shorter on hemodialysis treatment than non-BEN patients. As previous studies showed that the kidneys contribute to Epo elimination in a very minor fashion 35 and residual kidney function in patients more than three years on dialysis is most often negligible, it is not expected that renal elimination of Epo could be of any influence.

These findings need to be confirmed reckmbinante a well-controlled study with a larger sample size in order to establish population pharmacokinetics of beta-Epo in BEN patients, to evaluate the effects of physiopathological factors on the disposition kinetics of beta-Epo and to find potential predictive factors for dosage individualization.

The authors declare that they have no conflicts of interest related to the contents of this article. Endemic nephropathy in Bosnia.

Eritropoyetina Humana Recombinante –

Ciba Foundation Study Group No. Endemic recombinatne in Yugoslavia. Endemic Balkan Nephropathy, Proc. Der Mechanismus der Anaemie bie der endemische Nephropathie. Renal function, protein excretion and pathology of Balkan endemic nephropathy.

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J Am Soc Nephrol ; Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator C. Clin J Am Soc Nephrol ;1: Comparison of two recombinant erythropoietin formulations in patients with anemia due to end-stage renal disease on hemodialysis: A comparison of the bioequivalence of two formulations of epoetin alfa after subcutaneous injection.

Br J Clin Pharmacol ; Recombinant pharmacokinetics of recombinant human erythropoietin after subcutaneous injection at different sites.

Eur J Clin Pharmacol ; Population pharmacokinetics and pharmacodynamics of peptidic erythropoiesis receptor agonist ERA in healthy volunteers. J Clin Pharmacol ; J Clin Pharmacol Population pharmacokinetics of darbepoetin alfa in peritoneal dialysis recombibante non-dialysis patients with chronic kidney disease after single subcutaneous administration.

European best practice guidelines working group: