Drug Investigation

, Volume 8, Issue 5, pp 278–287 | Cite as

Pharmacokinetics of Epoetin in Dialysis Patients Before and After Correction of the Anaemia

  • Jens Dam Jensen
  • J. K. Madsen
  • L. W. Jensen
  • E. B. Pedersen
Original Research Article


The purpose of this study was to investigate the influence of prolonged treatment with recombinant human erythropoietin (epoetin) on the pharmacokinetics of epoetin in dialysis patients. 12 patients (male/female: 6/6, median age 44 years) with end-stage renal failure were investigated. Five were treated with continuous ambulatory peritoneal dialysis and 7 with haemodialysis. The pharmacokinetics were studied in each patient after an intravenous and a subcutaneous dose of epoetin 100 U/kg before regular treatment with epoetin was instituted. The investigation was repeated in the same patients after a median of 8 months of regular epoetin treatment. The haematocrit count increased from 25 to 33% (medians). The intravenous elimination half-life (8.23 vs 7.96 hours), intravenous mean residence time (11.8 vs 11.2 hours), clearance (0.31 vs 0.32 L/h/1.73 m2), subcutaneous maximal concentration (108 vs 123 U/L) at 19 vs 12 hours, and bioavailability (20.8 vs 21.6%) did not change significantly after prolonged epoetin treatment. The volume of distribution was slightly reduced from 3.76 to 3.46 L/1.73m2. The estimated absorption half-life (25.1 vs 16.7 hours), the mean input time (29.0 vs 29.9 hours), and the mean residence time (42.5 vs 40.1 hours) after subcutaneous application did not change significantly. The estimated endogenous epoetin production was unchanged at 144 vs 155 U/day/1.73m. The loss of epoetin in the peritoneal dialysis bags was below 2.3% of the dose.

In conclusion, except for a small reduction in the volume of distribution, long term treatment with epoetin had no influence on the intravenous or subcutaneous pharmacokinetics of epoetin in dialysis patients. No compensatory adjustment of the native epoetin production was detected.


Drug Invest Mean Residence Time Continuous Ambulatory Peritoneal Dialysis Recombinant Human Erythropoietin Continuous Ambulatory Peritoneal Dialysis Patient 


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  1. 1.
    Bommer J, Barth HP, Zeier M, et al. Efficacy comparison of intravenous and subcutaneous recombinant human erythropoietin administration in hemodialysis patients. Contrib Nephrol 1991; 88: 136–43PubMedGoogle Scholar
  2. 2.
    Eschbach JW, Kelly MR, Haley NR, et al. Treatment of the anemia of progressive renal failure with recombinant human erythropoietin. N Engl J Med 1989; 321: 158–63PubMedCrossRefGoogle Scholar
  3. 3.
    Boelaert JR, Schurgers ML, Matthys EG, et al. Comparative pharmacokinetics of recombinant erythropoietin administered by the intravenous, subcutaneous, and intraperitoneal routes in continuous ambulatory peritoneal dialysis (CAPD) patients. Perit Dial Int 1989; 9: 95–8PubMedGoogle Scholar
  4. 4.
    Kampf D, Kahl A, Passlick J, et al. Single-dose kinetics of recombinant human erythropoietin after intravenous, subcutaneous and intraperitoneal administration. Preliminary results. Contrib Nephrol 1989; 76: 106–10PubMedGoogle Scholar
  5. 5.
    Neumayer HH, Brockmoller J, Fritschka E, et al. Pharmacokinetics of recombinant human erythropoietin after SC administration and in long-term IV treatment in patients on maintenance hemodialysis. Contrib Nephrol 1989; 76: 131–41PubMedGoogle Scholar
  6. 6.
    Salmonson T, Danielson BG, Grahnen A, et al. Pharmacokinetics of intravenous recombinant human erythropoietin in patients with chronic renal failure. J Intern Med 1990; 228: 53–7PubMedCrossRefGoogle Scholar
  7. 7.
    Cotes PM, Pippard MJ, Reid CD, et al. Characterization of the anaemia of chronic renal failure and the mode of its correction by a preparation of human erythropoietin (r-HuEPO). An investigation of the pharmacokinetics of intravenous erythropoietin and its effects on erythrokinetics. Q J Med 1989; 70: 113–37PubMedGoogle Scholar
  8. 8.
    Lim VS, DeGowin RL, Zavala D, et al. Recombinant human erythropoietin treatment in pre-dialysis patients. A double-blind placebo-controlled trial. Ann Intern Med 1989; 110: 108–14PubMedGoogle Scholar
  9. 9.
    Brockmöller J, Köchling J, Weber W, et al. The pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in haemodialysis patients. Br J Clin Pharmac 1992; 34: 499–508Google Scholar
  10. 10.
    Annable L, Cotes PM, Musset MV. The second international preparation of erythropoietin, human, urinary for bioassay. Bull World Hlth Org 1972; 47: 99–112Google Scholar
  11. 11.
    Dunne A. Statistical moments in pharmacokinetics: models and assumptions. J Pharm Pharmacol 1993; 45: 871–5PubMedCrossRefGoogle Scholar
  12. 12.
    Yamaoka K, Nakagawa T, Uno T. Statistical moments in pharmacokinetics. J Pharmakinet Biopharm 1978; 6: 547–58Google Scholar
  13. 13.
    Handbook of basic pharmacokinetics. 3rd ed. Illinios: Hamilton, 1986: 282–301Google Scholar
  14. 14.
    Handbook of basic pharmacokinetics. 3rd ed. Illinois: Hamilton, 1986: 462–94Google Scholar
  15. 15.
    Wagner JG. Pharmacokinetics and bioavailability. Triangle 1973; 14: 101–8Google Scholar
  16. 16.
    Boxenbaum HG, Riegelman S, Elashoff M. Statistical estimations in pharmacokinetics. J Pharmakinet Biopharm 1974; 2: 123–48Google Scholar
  17. 17.
    McMahon FG, Vargas R, Ryan M, et al. Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers. Blood 1990; 76: 1718–22PubMedGoogle Scholar
  18. 18.
    Spivak JL, Hogans BB. The in vivo metabolism of recombinant human erythropoietin in the rat. Blood 1989; 73: 90–9PubMedGoogle Scholar
  19. 19.
    Adamson JW, Alexanian R, Martinez C, et al. Erythropoietin excretion in normal man. Blood 1966; 28: 354–64PubMedGoogle Scholar
  20. 20.
    Alexanian R. Urinary excretion of erythropoietin in normal men and women. Blood 1966; 28: 344–53PubMedGoogle Scholar
  21. 21.
    Mayeux P, Billat C, Jacquot R. The erythropoietin receptor of rat erythroid progenitor lens. Characterization and affinity cross-linkage. J Biol Chem 1987; 262: 13985–90PubMedGoogle Scholar
  22. 22.
    Sawyer ST, Krantz SB, Goldwasser E. Binding and receptormediated endocytosis of erythropoietin in Friend virus-infected erythroid cells. J Biol Chem 1987; 262: 5554–62PubMedGoogle Scholar
  23. 23.
    Piroso E, Erslev AJ, Flaharty KK, et al. Erythropoietin life span in rats with hypoplastic and hyperplastic bone marrows. Am J Hematol 1991; 36: 105–10PubMedCrossRefGoogle Scholar
  24. 24.
    Naets JP, Wittek M. Effect of erythroid hyperplasia on the disappearance rate of erythropoietin in the dog. Acta Haematol 1968; 39: 42–50PubMedCrossRefGoogle Scholar
  25. 25.
    Macdougall IC, Roberts DE, Neubert P, et al. Pharmacokinetics of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis [see comments]. Lancet 1989; 1: 425–7PubMedCrossRefGoogle Scholar
  26. 26.
    Kampf D, Eckardt KU, Fischer HC, et al. Pharmacokinetics of recombinant human erythropoietin in dialysis patients after single and multiple subcutaneous administrations. Nephron 1992; 61: 393–8PubMedCrossRefGoogle Scholar
  27. 27.
    Macdougall IC, Jones JM, Robinson MI, et al. Subcutaneous erythropoietin therapy: comparison of three different sites of injection. Contrib Nephrol 1991; 88: 152–6PubMedGoogle Scholar
  28. 28.
    Nielsen OJ. Pharmacokinetics of recombinant human erythropoietin in chronic haemodialysis patients. Pharmacol Toxicol 1990; 66: 83–6PubMedCrossRefGoogle Scholar
  29. 29.
    Salmonson T, Danielson BG, Wikstrom B. The pharmacokinetics of recombinant human erythropoietin after intravenous and subcutaneous administration to healthy subjects. Br J Clin Pharmacol 1990; 29: 709–13PubMedCrossRefGoogle Scholar
  30. 30.
    Hughes RT, Cotes PM, Pippard MJ, et al. Subcutaneous administration of recombinant human erythropoietin to subjects on continuous ambulatory peritoneal dialysis: an erythrokinetic assessment. Br J Haematol 1990; 75: 268–73PubMedCrossRefGoogle Scholar
  31. 31.
    Jensen JD, Madsen JK, Jensen LW, et al. Reduced production, absorption, and elimination of erythropoietin in uremia compared with healthy volunteers. J Am Soc Nephrol 1994; 5: 177–85PubMedGoogle Scholar
  32. 32.
    Halstenson CE, Macres M, Katz SA, et al. Comparative pharmacokinetics and pharmacodynamics of epoetin alfa and epoetin beta. Clin Pharmacol Ther 1991; 50: 702–12PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Jens Dam Jensen
    • 1
  • J. K. Madsen
    • 1
  • L. W. Jensen
    • 1
  • E. B. Pedersen
    • 1
  1. 1.Department of Nephrology and Medicine C, Skejby HospitalUniversity Hospital in AarhusAarhusDenmark

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