Arzneimittelforschung 2008; 58(5): 215-219
DOI: 10.1055/s-0031-1296497
Therapeutics for States of Deficiency
Editio Cantor Verlag Aulendorf (Germany)

Evaluation of the Pharmacokinetics of Two Recombinant Human Erythropoietin Preparations: Epoetin Zeta and Epoetin Alfa

1st Communication: A monocentric, open, randomized, single dose, two-period crossover trial in healthy volunteers
Valentin Kirkov
1   University Hospital “Queen Giovanna”, Sofia, Bulgaria
Velislava Dimitrova
2   University Hospital “Sveti Ivan Rilski”, Sofia, Bulgaria
Marianne Siebert-Weigel
3   STADA R&D GmbH, Bad Vilbel, Germany
Michael Wolf-Pflugmann
3   STADA R&D GmbH, Bad Vilbel, Germany
Rossen Koytchev
4   Cooperative Clinical Drug Research and Development (CCDRD) AG, Neuenhagen, Germany
Wolfram Richter
4   Cooperative Clinical Drug Research and Development (CCDRD) AG, Neuenhagen, Germany
Angelika Bronn
4   Cooperative Clinical Drug Research and Development (CCDRD) AG, Neuenhagen, Germany
Sacha Arsova
4   Cooperative Clinical Drug Research and Development (CCDRD) AG, Neuenhagen, Germany
Arno Kromminga
5   IPM GmbH, Hamburg, Germany
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15. Dezember 2011 (online)


The pharmacokinetic properties of a new recombinant erythropoietin preparation (epoetin zeta, CAS 604802-70-2) compared to a reference product (epoetin alfa, CAS 113427-24-0) were analyzed after a single intravenous bolus injection of 10,000 IU in a two-period crossover design in 24 healthy volunteers. Peripheral venous blood samples were obtained pre-dose, and 0:05, 0:20, 0:40, 1:00, 1:20, 1:40, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 36:00, 48:00, and 72:00 hours post dosing. Samples of 24 volunteers were analyzed by means of a specific immunoassay (ELISA).

Three volunteers were excluded from statistical analysis due to a paravasal injection in one of both study periods with resulting low plasma levels of epoetin.

Comparison of both preparations showed nearly identical pharmacokinetic properties after intravenous administration. The usual bioequivalence limits were fulfilled for all relevant pharmacokinetic parameters.

  • Literature

  • 1 Juul SE, Yachnis AT, Christensen RD. Tissue distribution of erythropoietin and erythropoietin receptor in the developing human fetus. Early Hum Dev. 1998; 52: 235-249
  • 2 Bodó E, Kromminga A, Funk W, Laugsch M, Duske U, Jelkmann W et al. Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin. FASEBJ. 2007; Oct 21 (12) 3346-3354
  • 3 Ridley DM, Dawkins F, Perlin E. Erythropoietin: A review. J Natl Med Assoc. 1994; 86 (2) 129-135
  • 4 Wang GL, Semenza GL. Molecular basis of hypoxia-induced erythropoietin expression. Curr Opin Hematol. 1996; 3: 156-162
  • 5 Lacombe C, Mayeux P. The molecular biology of erythropoietin. Nephrol Dial Transplant. 1999; 14 (2) 22-28
  • 6 Summary of Product Characteristics: Erypo®/Erypo® FS. Neuss (Germany): Janssen-Cilag GmbH; December 2002.
  • 7 Demain AL. Microbial biotechnology. Tibtech. 2000; 18: 26-31
  • 8 Macdougall IC. Treatment of renal anemia with recombinant human erythropoietin. Curr Opin Nephrol Hypertens. 1992; 1: 210-219
  • 9 ICH Topic E 6. Guideline for Good Clinical Practice. Step 5, Consolidated Guideline from 01.05.1996. Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95). Jan 1997.
  • 10 FDA Guidance for Industry. Bioanalytical Method Validation. May 2001.
  • 11 Shah VP, Midha KK, Findlay JWA, Hill HM, Hulse JD, McGilveray IJ et al. Bioanalytical Method Validation – A Revist with a Decade of Progress. Pharm Res. 2000; 17: 1551-1557
  • 12 McMahon FG, Vargas R, Ryan M, Jain AK, Abels RI, Perry B et al. Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers. Blood. 1990; Nov 76: 1718-1722