Change in erythropoietin pharmacokinetics following hematopoietic transplantation

J. A. Widness, R. L. Schmidt, Raymond Hohl, F. D. Goldman, N. H. Al-Huniti, K. J. Freise, P. Veng-Pedersen

Research output: Contribution to journalArticle

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Abstract

Pre-clinical studies have demonstrated that bone marrow ablation has a profound effect in decreasing erythropoietin (EPO) elimination. The study's objective was to determine in humans if EPO pharmacokinetics (PKs) are perturbed following bone marrow ablation. EPO PK studies were performed in eight subjects, aged 4 to 61 years, undergoing fully myeloablative hematopoietic stem cell transplantation. Serial PK studies using intravenous injection of recombinant human EPO (92±2.0 U/kg) (mean±SEM) were carried out during four periods of altered marrow integrity: baseline pre-ablation, post-ablation pre-transplant, early post-transplant pre-engraftment, and late post-transplant full engraftment. Compared with baseline, post-ablation pre-transplant and early post-transplant EPO PKs demonstrated declines in clearance increases in terminal elimination half-life of 36 and 95%, respectively. Clearance and half-life returned to baseline following full engraftment. The association of EPO elimination with decreased bone marrow activity in patients undergoing transplantation conclusively establishes the bone marrow as a key determinant of EPO elimination in humans.

Original languageEnglish (US)
Pages (from-to)873-879
Number of pages7
JournalClinical pharmacology and therapeutics
Volume81
Issue number6
DOIs
StatePublished - Jun 1 2007

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Erythropoietin
Pharmacokinetics
Transplantation
Bone Marrow
Transplants
Half-Life
Hematopoietic Stem Cell Transplantation
Intravenous Injections

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Widness, J. A., Schmidt, R. L., Hohl, R., Goldman, F. D., Al-Huniti, N. H., Freise, K. J., & Veng-Pedersen, P. (2007). Change in erythropoietin pharmacokinetics following hematopoietic transplantation. Clinical pharmacology and therapeutics, 81(6), 873-879. https://doi.org/10.1038/sj.clpt.6100165
Widness, J. A. ; Schmidt, R. L. ; Hohl, Raymond ; Goldman, F. D. ; Al-Huniti, N. H. ; Freise, K. J. ; Veng-Pedersen, P. / Change in erythropoietin pharmacokinetics following hematopoietic transplantation. In: Clinical pharmacology and therapeutics. 2007 ; Vol. 81, No. 6. pp. 873-879.
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Widness, JA, Schmidt, RL, Hohl, R, Goldman, FD, Al-Huniti, NH, Freise, KJ & Veng-Pedersen, P 2007, 'Change in erythropoietin pharmacokinetics following hematopoietic transplantation', Clinical pharmacology and therapeutics, vol. 81, no. 6, pp. 873-879. https://doi.org/10.1038/sj.clpt.6100165

Change in erythropoietin pharmacokinetics following hematopoietic transplantation. / Widness, J. A.; Schmidt, R. L.; Hohl, Raymond; Goldman, F. D.; Al-Huniti, N. H.; Freise, K. J.; Veng-Pedersen, P.

In: Clinical pharmacology and therapeutics, Vol. 81, No. 6, 01.06.2007, p. 873-879.

Research output: Contribution to journalArticle

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