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Arzneimittelforschung 2008; 58(5): 220-224
DOI: 10.1055/s-0031-1296498
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

2nd Communication: A monocentric, double-blind, randomized, single dose, three-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
› Author Affiliations
Further Information

Publication History

Publication Date:
15 December 2011 (online)

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Abstract

The subcutaneous bioavailability of a new recombinant erythropoietin preparation (epoetin zeta, CAS 604802-70-2) and the pharmacokinetic properties of this drug compared to a reference product (epoetin alfa, CAS 113427-24-0) were analyzed after a single intravenous bolus injection or subcutaneous injection of 10,000 IU in a three-period crossover design in 48 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 h post dosing. Samples from 48 volunteers were analyzed by means of a specific immunoassay (ELISA).

The systemic bioavailability of epoetin zeta after subcutaneous administration is approximately 24 %. Comparison of both preparations showed nearly identical pharmacokinetic properties after subcutaneous administration. The usual bioequivalence limits were fulfilled for all relevant pharmacokinetic parameters.

Key words

CAS 113427-24-0 - CAS 604802-70-2 - Epoetin alfa, bioavailability, bioequivalence, biosimilar, pharmacokinetics - Epoetin zeta, bioavailability, bioequivalence, biosimilar, pharmacokinetics

*) 1st Communication: Arzneimittel-Forschung (Drug Research) 2008;58(5):215–219.


 

  • References

  • 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
    CrossrefPubMedGoogle Scholar
  • 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) 3346-54
    CrossrefPubMedGoogle Scholar
  • 3 Ridley. Dawkins F, Perlin E. Erythropoietin: A review. J Natl MedAssoc. 1994; 86 (2) 129-135
    PubMedGoogle Scholar
  • 4 Wang GL, Semenza GL. Molecular basis of hypoxia-induced erythropoietin expression. Curr Opin Hematol. 1996; 3: 156-162
    CrossrefPubMedGoogle Scholar
  • 5 Lacombe C, Mayeux P. The molecular biology of erythropoietin. Nephrol Dial Transplant. 1999; 14 (2) 22-28
    PubMedGoogle Scholar
  • 6 Summary of Product Characteristics: Erypo®/Erypo® FS. Neuss (Germany): Janssen-Cilag GmbH; December 2002.
    PubMed
  • 7 Demain AL. Microbial biotechnology. Tibtech. 2000; 18: 26-31
    CrossrefPubMedGoogle Scholar
  • 8 Macdougall IC. Treatment of renal anemia with recombinant human erythropoietin. Curr Opin Nephrol Hypertens. 1992; 1: 210-219
    CrossrefPubMedGoogle Scholar
  • 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.
    PubMed
  • 10 FDA Guidance for Industry. Bioanalytical Method Validation. May 2001.
    PubMed
  • 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
    CrossrefPubMedGoogle Scholar