title: Comparison of two recombinant erythropoietin formulations in patients with anemia due to end-stage renal disease on hemodialysis: a parallel, randomized, double blind study.
abstract: BACKGROUND
  Recombinant 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Both 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.
  
  
  CONCLUSIONS
  The formulations are comparable. The newly developed product should be acceptable for long-term application.
authors.affiliation: Hemodialysis Department, National Institute of Nephrology, Havana, Cuba. jfpolivd@infomed.sld.cu
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Pérez-Oliva
authors.forename: Martha
authors.initials: M
authors.lastname: Casanova-González
authors.forename: Idrian
authors.initials: I
authors.lastname: García-García
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Porrero-Martín
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Valenzuela-Silva
authors.forename: Tairí
authors.initials: T
authors.lastname: Hernández-Montero
authors.forename: Marcia
authors.initials: M
authors.lastname: Lagarde-Ampudia
authors.forename: Yuri
authors.initials: Y
authors.lastname: Casanova-Kutsareva
authors.forename: Yisel
authors.initials: Y
authors.lastname: Avila-Albuerne
authors.forename: Alicia
authors.initials: A
authors.lastname: Vargas-Batista
authors.forename: Hailen
authors.initials: H
authors.lastname: Bobillo-López
authors.forename: Raúl
authors.initials: R
authors.lastname: Herrera-Valdés
authors.forename: Pedro A
authors.initials: PA
authors.lastname: López-Saura
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology*; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006397:Hematinics / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa