Skip to main content
SpringerLink
Log in

Clinical pharmacokinetic properties of rHuEPO: a review

  • Chapter
Erythropoietins and Erythropoiesis

Part of the book series: Milestones in Drug Therapy MDT ((MDT))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Brockmöller J, Kochling J, Weber W, Looby M, Roots I, Neumayer HH (1992) The pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in haemodialysis patients. Br J Clin Pharmacol 34: 499–508

    PubMed  Google Scholar 

  2. Kampf D, Eckardt KU, Fischer HC, Schmalisch C, Ehmer B, Schostak M (1992) Pharmacokinetics of recombinant human erythropoietin in dialysis patients after single and multiple subcutaneous administrations. Nephron 61: 393–398

    CAS  PubMed  Google Scholar 

  3. Wide L, Bengtsson C, Birgegard G (1989) Circadian rhythm of erythropoietin in human serum. Br J Haematol 72: 85–90

    CAS  PubMed  Google Scholar 

  4. Cheung WK, Goon BL, Guilfoyle MC, Wacholtz MC (1998) Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin after single and multiple subcutaneous doses to healthy subjects. Clin Pharmacol Ther 64: 412–423

    Article  CAS  PubMed  Google Scholar 

  5. Schouten JP, Voorhorst G, Helbing AR, Janssen JW, Diderich PP, Op de Hoek CT (1993) Pharmacokinetics of epoetin in haemodialysis patients after subcutaneous administration: Influence of chronic treatment. Pharm World Sci 15: 252–256

    Article  CAS  PubMed  Google Scholar 

  6. Gladziwa U, Klotz U, Baumer K, Zollinger R, Mann H, Sieberth HG (1993) Pharmacokinetics of epoetin (recombinant human erythropoietin) after long term therapy in patients undergoing haemodialysis and haemofiltration. Clin Pharmacokinet 25: 145–153

    CAS  PubMed  Google Scholar 

  7. Halstenson CE, Macres M, Katz SA, Schnieders JR, Watanabe M, Sobota JT, Abraham PA (1991) Comparative pharmacokinetics and pharmacodynamics of epoetin alfa and epoetin beta. Clin Pharmacol Ther 50: 702–712

    CAS  PubMed  Google Scholar 

  8. Nielsen OJ (1990) Pharmacokinetics of recombinant human erythropoietin in chronic haemodialysis patients. Pharmacol Toxicol 66: 83–86

    CAS  PubMed  Google Scholar 

  9. Salmonson T, Danielson BG, Grahnen A, Wikstrom B (1990) Pharmacokinetics of intravenous recombinant human erythropoietin in patients with chronic renal failure. J Intern Med 228: 53–57

    CAS  PubMed  Google Scholar 

  10. Boelaert JR, Schurgers ML, Matthys EG, Belpaire FM, Daneels RF, De Cre MJ, Bogaert MG (1989) Comparative pharmacokinetics of recombinant erythropoietin administered by the intravenous, subcutaneous, and intraperitoneal routes in continuous ambulatory peritoneal dialysis (CAPD) patients. Perit Dialy Int 9: 95–98

    CAS  Google Scholar 

  11. Urabe A, Takaku F, Mizoguchi H, Kubo K, Ota K, Shimizu N, Tanaka K, Mimura N, Nihei H, Koshikawa S (1988) Effect of recombinant human erythropoietin on the anemia of chronic renal failure. Int J Cell Cloning 6: 179–191

    CAS  PubMed  Google Scholar 

  12. Cheung WK, Natarajan J, Sanders M, Vercammen E (2000) Comparative pharmacokinetics, safety, and tolerability after subcutaneous administration of recombinant human erythropoietin formulated with different stabilizers. Biopharm Drug Dispos 21: 211–219

    Article  CAS  PubMed  Google Scholar 

  13. Ateshkadi A, Johnson CA, Oxton LL, Hammond TG, Bohenek WS, Zimmerman SW (1993) Pharmacokinetics of intraperitoneal, intravenous, and subcutaneous recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 21: 635–642

    CAS  PubMed  Google Scholar 

  14. Flaharty KK, Caro J, Erslev A, Whalen JJ, Morris EM, Bjornsson TD, Vlasses PH (1990) Pharmacokinetics and erythropoietic response to human recombinant erythropoietin in healthy men. Clin Pharmacol Ther 47: 557–564

    PubMed  Google Scholar 

  15. McMahon FG, Vargas R, Ryan M, Jain AK, Abels RI, Perry B, Smith IL (1990) Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers. Blood 76: 1718–1722

    CAS  PubMed  Google Scholar 

  16. Jensen JD, Madsen JK, Jensen LW, Pedersen EB (1994) Pharmacokinetics of epoetin in dialysis patients before and after correction of the anaemia. Drug Investigation 8: 278–287

    Google Scholar 

  17. Jensen JD, Jensen LW, Madsen JK, Poulsen L (1995) The metabolism of erythropoietin in liver cirrhosis patients compared with healthy volunteers. Eur J Haematol 54: 111–116

    CAS  PubMed  Google Scholar 

  18. Jensen JD, Madsen JK, Jensen LW, Pedersen EB (1994) Reduced production, absorption, and elimination of erythropoietin in uremia compared with healthy volunteers. J Am Soc Nephrol 5:177–185

    CAS  PubMed  Google Scholar 

  19. Veng-Pedersen P, Widness JA, Pereira LM, Peters C, Schmidt RL, Lowe LS (1995) Kinetic evaluation of nonlinear drug elimination by a disposition decomposition analysis. Application to the analysis of the nonlinear elimination kinetics of erythropoietin in adult humans. J Pharm Sci 84:760–767

    CAS  PubMed  Google Scholar 

  20. Salmonson T, Danielson BG, Wikstrom B (1990) The pharmacokinetics of recombinant human erythropoietin after intravenous and subcutaneous administration to healthy subjects. Br J Clin Pharmacol 29: 709–713

    CAS  PubMed  Google Scholar 

  21. Souillard A, Audran M, Bressolle F, Gareau R, Duvallet A, Chanal JL (1996) Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in athletes. Blood sampling and doping control. Br J Clin Pharmacol 42: 355–364

    Article  CAS  PubMed  Google Scholar 

  22. Sans T, Joven J, Vilella E, Masdeu G, Farre M (2000) Pharmacokinetics of several subcutaneous doses of erythropoietin: potential implications for blood transfusion. Clin Exp Pharmacol Physiol 27: 179–184

    Article  CAS  PubMed  Google Scholar 

  23. Hayashi N, Kinoshita H, Yukawa E, Higuchi S (1998) Pharmacokinetic analysis of subcutaneous erythropoeitin administration with nonlinear mixed effect model including endogenous production. Br J Clin Pharmacol 46: 11–19

    Article  CAS  PubMed  Google Scholar 

  24. Kindler J, Eckardt KU, Ehmer B, Jandeleit K, Kurtz A, Schreiber A, Scigalla P, Sieberth HG (1989) Single-dose pharmacokinetics of recombinant human erythropoietin in patients with various degrees of renal failure. Nephrol Dial Transplant 4: 345–349

    CAS  PubMed  Google Scholar 

  25. Neumayer HH, Brockmöller J, Fritschka E, Roots I, Scigalla P, Wattenberg M, (1989) Pharmacokinetics of recombinant human erythropoietin after SC administration and in long-term IV treatment in patients on maintenance hemodialysis. Contrib Nephrol 76: 131–141

    CAS  PubMed  Google Scholar 

  26. Macdougall IC, Roberts DE, Neubert P, Dharmasena AD, Coles GA, Williams JD (1989) Pharmacokinetics of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. Lancet 1: 425–427

    CAS  PubMed  Google Scholar 

  27. Hughes RT, Cotes PM, Oliver DO, Pippard MJ, Royston P, Stevens JM, Strong CA, Tam RC (1989) Correction of the anaemia of chronic renal failure with erythropoietin: Pharmacokinetic studies in patients on haemodialysis and CAPD. Contrib Nephrol 76: 122–130

    CAS  PubMed  Google Scholar 

  28. Egrie JC, Eschbach JW, McGuire T, Adamson JW (1988) Pharmacokinetics of recombinant human erythropoietin (rHuEpo) administered to hemodialysis (HD) patients. Kidney Int 33: abstract, p. 262

    Google Scholar 

  29. Cotes JM, Pippard MJ, Reid CD, Winearls CG, Oliver DP, Royston JP (1989) 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 70: 113–137

    CAS  PubMed  Google Scholar 

  30. Kampf D, Kahl A, Passlick J, Pustelnik A, Eckardt KU, Ehmer B, Jacobs C, Baumelou A, Grabensee B, Gahl GM (1989) Single-dose kinetics of recombinant human erythropoietin after intravenous, subcutaneous and intraperitoneal administration. Preliminary results. Contrib Nephrol 76: 106–110

    CAS  PubMed  Google Scholar 

  31. Lim VS, DeGowin RL, Zavala D, Kirchner PT, Abels R, Perry P, Fangman J (1989) Recombinant human erythropoietin treatment in pre-dialysis patients. A double-blind placebo-controlled trial. Ann Intern Med 110: 108–114

    CAS  PubMed  Google Scholar 

  32. Krömer G, Solf A, Ehmer B, Kaufmann B, Quellhorst E (1990) Single dose pharmacokinetics of recombinant human erythropoietin (rhEPO) comparing intravenous (IV), subcutaneous (SC) and intraperitoneal (IP) administration in ipd patients. Kidney Int 37: 331

    Google Scholar 

  33. Stockenhuber F, Loibl U, Gottsauner-Wolf M, Jahn C, Manker W, Meisl TF, Balcke (1991) Pharmacokinetics and dose response after intravenous and subcutaneous administration of recombinant erythropoietin in patients on regular haemodialysis treatment or continuous ambulatory peritoneal dialysis. Nephron 59: 399–402

    CAS  PubMed  Google Scholar 

  34. Yamazaki C, Watanabe Y, Sakamoto N (1993) Pharmacokinetic study of recombinant human erythropoietin treatment in pre-dialysis end stage renal disease patients. Nippon Jinzo Gakkai Shi 35:1233–1242

    CAS  PubMed  Google Scholar 

  35. Petersen J, Kang MS, Hays MT (1996) Erythropoietin can be administered during dialysis: A kinetic analysis. ASAIO J 42: 27–33

    CAS  PubMed  Google Scholar 

  36. Bargman JM, Jones JE, Petro JM (1992) The pharmacokinetics of intraperitoneal erythropoietin administered undiluted or diluted in dialysate. Perit Dial Int 12: 369–372

    CAS  PubMed  Google Scholar 

  37. Taylor CA III, Kosorok MR, Zimmerman SW, Johnson CA (1999) Pharmacokinetics of intraperitoneal epoetin alfa in patients on peritoneal dialysis using an 8-hour “dry dwell” dosing technique. Am J Kidney Dis 34: 657–662

    CAS  PubMed  Google Scholar 

  38. Reddingius RE, Schroder CH, Koster AM, Monnens LA (1994) Pharmacokinetics of recombinant human erythropoietin in children treated with continuous ambulatory peritoneal dialysis. Eur J Pediatr 153: 850–854

    CAS  PubMed  Google Scholar 

  39. Evans JH, Brockleank JT, Bowmer CJ, Ng PC (1991) Pharmacokinetics of recombinant human erythropoietin in children with renal failure. Nephrol Dial Transplant 6: 709–714

    CAS  PubMed  Google Scholar 

  40. Montini G, Zacchello G, Perfumo F (1991) Pharmacokinetics and pharmacodynamis of subcutaneous administration of r-HuEPO on CPD. A multicenter study from the Italian Registry of Pediatric CPD. J Am Soc Nephrol 2: 283

    Google Scholar 

  41. Braun A, Ding R, Seidel C, Fies T, Kurtz A, Scharer K (1993) Pharmacokinetics of recombinant human erythropoietin applied subcutaneously to children with chronic renal failure. Pediatric Nephrol 7: 61–64

    Article  CAS  Google Scholar 

  42. Geva P, Sherwood JB (1991) Pharmacokinetics of recombinant human erythropoietin (rHuEPO) in pediatric patients on chronic cycling peritoneal dialysis (CCPD). Blood 78(Suppl. 1): 91a

    Google Scholar 

  43. Cakar N, Ekim M, Turner N, Yalcinkaya F, Akar N, Onaran HO (1997) Pharmacokinetics of recombinant human erythropoietin in children with chronic renal failure. Int Urol Nephrol 29:377–383

    CAS  PubMed  Google Scholar 

  44. Jabs K, Grant JR, Harmon W, Egrie JC (1991) Pharamcokinetics of Epoetin Alfa (rHuEPO) in pediatric hemodialysis (HD) patients. J Am Soc Nephrol 2: 380

    Google Scholar 

  45. Kausz AT, Watkins SL, Hansen C, Godwin DA, Palmer RB, Brandt JR (1999) Intraperitoneal erythropoietin in children on peritoneal dialysis: A study of pharmacokinetics and efficacy. Am J Kidney Dis 34: 651–656

    CAS  PubMed  Google Scholar 

  46. Jobs K, Grenda R, Gregorek H (1995) Pain relief and correct erythropoietin kinetics after Eprex injection with EMLA (lignocaine-prilocaine cream) premedication in dialysed children. Ann Acad Med Gedanesis 25: 93–97

    CAS  Google Scholar 

  47. Canaparo R, Casale F, Muntoni E, Zara GP, Della Pepa C, Berno E, Pons N, Fornari G, Eandi M (2000) Plasma erythropoietin concentrations in patients receiving intensive platinum or nonplatinum chemotherapy. Br J Clin Pharmacol 50: 146–153

    Article  CAS  PubMed  Google Scholar 

  48. Pedain C, Herrero J, Kunzel W (2001) Serum erythropoietin levels in ovarian cancer patients receiving chemotherapy. Eur J Obstet Gynecol Reprod Biol 98: 224–230

    Article  CAS  PubMed  Google Scholar 

  49. Franek E, Wiecek A, Kozielski J, Rauer R, Kokot M, Kokot F, Oklek K (1996) [Half-time of erythropoietin in patients with chronic obstructive pulmonary diseases]. Przegl Lek 53: 592–594

    CAS  PubMed  Google Scholar 

  50. Bowen D, Ehmer B, Neubert P, Lewis T, Jacobs A (1991) The clearance of a single i.v. bolus of recombinant human erythropoietin from the serum of patients with myelodysplastic syndromes and its effects on erythropoiesis. Exp Hematol 19: 613–616

    CAS  PubMed  Google Scholar 

  51. Macdougall IC, Jones JM, Robinson MI, Miles JB, Coles GA, Williams JD (1991) Subcutaneous erythropoietin therapy: comparison of three different sites of injection. Contrib Nephrol 88:152–156

    CAS  PubMed  Google Scholar 

  52. Jensen JD, Jensen LW, Madsen JK (1994) The pharmacokinetics of recombinant human erythropoietin after subcutaneous injection at different sites. Eur J Clin Pharmacol 46: 333–337

    Article  CAS  PubMed  Google Scholar 

  53. Storring PL, Tiplady RJ, Gaines Das RE, Stenning BE, Lamikanra A, Rafferty B, Lee J (1998) Epoetin alfa and beta differ in their erythropoietin isoform compositions and biological properties. Br J Haematol 100: 79–89

    CAS  PubMed  Google Scholar 

  54. Kato M, Kamiyama H, Okazaki A, Kumaki K, Kato Y, Sugiyama Y (1997) Mechanism for the nonlinear pharmacokinetics of erythropoietin in rats. J Pharmacol Exp Ther 283: 520–527

    CAS  PubMed  Google Scholar 

  55. Spivak JL, Hogans BB (1989) The in vivo metabolism of recombinant human erythropoietin in the rat. Blood 73: 90–99

    CAS  PubMed  Google Scholar 

  56. Macdougall IC, Gray SJ, Elston O, Breen C, Jenkins B, Browne J, Egrie J (1999) Pharmaceokinetics of novel erythropoieis stimulating protein compared with epoetin alfa in dialysis patients. J Am Soc Nephrol 10: 2392–2395

    CAS  PubMed  Google Scholar 

  57. Steinberg SE, Garcia JF, Matzke GR, Mladenovic J (1996) Erythropoietin kinetics in rats: generation and clearance. Blood 67: 646–649

    Google Scholar 

  58. Fu JS, Lertora JJL, Brookins J, Rice JC, Fisher JW (1988) Pharmacokinetics of erythropoietin in intact and anephric dogs. J Lab Clin Med 111: 669–676

    CAS  PubMed  Google Scholar 

  59. Dinkelaar RB, Engels EY, Hart AA, Schoemaker LP, Bosch E, Chamuleau RA (1981) Metabolic studies on erythropoietin (EP): II. The role of liver and kidney in the metabolism of EP. Exp Hematol 9: 796–803

    CAS  PubMed  Google Scholar 

  60. Fukuda MN, Sasaki H, Lopez L, Fukuda M (1989) Survival of recombinant erythropoietin in the circulation: The role of carbohydrates. Blood 73: 84–89

    CAS  PubMed  Google Scholar 

  61. Sawyer ST, Krantz SB, Goldwasser E (1987) Binding and receptor-mediated endocytosis of erythropoietin in Friend virus-infected erythroid cells. J Biol Chem 262: 5554–5562

    CAS  PubMed  Google Scholar 

  62. Kaufman JS, Reda DJ, Fye CL, Goldfarb DS, Henderson WG, Kleinman JG, Vaamonde CA (1998) Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. N Engl J Med 339: 578–583

    CAS  PubMed  Google Scholar 

  63. McLennan DN, Porter CJH, Edwards GA, Martin SW, Heatherington AC, Charman SA (2002) Lymphatic absorption is the primary contributor to the systemic availability of epoetin alpha following subcutaneous administration to sheep. American Association of Pharmaceutical Scientists National Meeting, Toronto

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Amgen Inc., One Amgen Center Drive, M/S 30E-0-A, Thousand Oaks, California, 91320, USA

    Anne C. Heatherington

Authors
  1. Anne C. Heatherington
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Amgen Inc, One Amgen Center Drive, Thousand Oaks, California, 91320, USA

    Graham Molineux , Mary Ann Foote  & Steven G. Elliott ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Birkhäuser Verlag/Switzerland

About this chapter

Cite this chapter

Heatherington, A.C. (2003). Clinical pharmacokinetic properties of rHuEPO: a review. In: Molineux, G., Foote, M.A., Elliott, S.G. (eds) Erythropoietins and Erythropoiesis. Milestones in Drug Therapy MDT. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7543-4_6

Download citation

Publish with us

Policies and ethics

Search

Navigation