Abstract
BackgroundRecombinant human erythropoietin (EPO) is used for the treatment of last stage renal anemia. A new EPO preparation was obtained in Cuba in order to make this treatment fully nationally available. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of two recombinant EPO formulations in patients with anemia due to end-stage renal disease on hemodialysis.MethodsA parallel, randomized, double blind study was performed. A single 100 IU/Kg EPO dose was administered subcutaneously. Heberitro (Heber Biotec, Havana, formulation A), a newly developed product and Eprex (CILAG AG, Switzerland, formulation B), as reference treatment were compared. Thirty-four patients with anemia due to end-stage renal disease on hemodialysis were included. Patients had not received EPO previously. Serum EPO level was measured by enzyme immunoassay (EIA) during 120 hours after administration. Clinical and laboratory variables were determined as pharmacodynamic and safety criteria until 216 hours.ResultsBoth groups of patients were similar regarding all demographic and baseline characteristics. EPO kinetics profiles were similar for both formulations; the pharmacokinetic parameters were very close (i.e., AUC: 4667 vs. 4918 mIU.h/mL; Cmax: 119.1 vs. 119.7 mIU/mL; Tmax: 13.9 vs. 18.1 h; half-life, 20.0 vs. 22.5 h for formulations A and B, respectively). The 90% confidence intervals for the ratio between both products regarding these metrics were close to the 0.8 – 1.25 range, considered necessary for bioequivalence. Differences did not reach 20% in any case and were not determined by a formulation effect, but probably by a patients' variability effect. Concerning pharmacodynamic features, a high similitude in reticulocyte counts increments until 216 hours and the percentage decrease in serum iron until 120 hours was observed. There were no differences between formulations regarding the adverse events and their intensity. The more frequent events were pain at injection site (35.3%) and hypertension (29%). Additionally, further treatment of the patients with the study product yielded satisfactory increases in hemoglobin and hematocrit values.ConclusionThe formulations are comparable. The newly developed product should be acceptable for long-term application.
Highlights
Recombinant human erythropoietin (EPO) is used for the treatment of last stage renal anemia
Recombinant human EPO has been used since the 80's in the treatment of anemia associated to end-stage renal disease
Thirty-four patients were recruited at the seven hospitals where they regularly received hemodialysis treatment
Summary
Recombinant human erythropoietin (EPO) is used for the treatment of last stage renal anemia. Erythropoietin (EPO) is a sialoglycoprotein hormone secreted primarily by the mature kidneys in response to tissue hypoxia and/or red cell mass decrease. It stimulates erythrocyte production from the blood marrow [1]. Whether multiorigin recombinant proteins can be clinically interchangeable despite coming from different strains and manufacturing processes is a controversial matter nowadays [9,10] If this principle is accepted, a study that shows pharmacological similarity between two products would be enough to indicate its therapeutic interchangeability, given that they are chemically and pharmaceutically equivalent as well
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