Pharmacokinetic tracer kinetics analysis of changes in erythropoietin receptor population in phylebotomy-induced anemia and bone marrow ablation

P. Veng-Pedersen, S. Chapel, N. H. Al-Huniti, R. L. Schimdt, E. M. Sedars, R. J. Hohl, J. A. Widness

Research output: Contribution to journalArticle

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Abstract

Objectives - The objective was to study in vivo erythropoietin (Epo) progenitor cell surface receptors (EpoR) in the bone marrow (BM) after phlebotomy and bone marrow ablation. Methods - Serial tracer interaction method experiments were conducted in adult sheep at baseline and after phlebotomy (PH) and ablation (AB). PH was done 10 days after phlebotomy (to 3-4g/dl Hb), and the AB was done 8 days after a 3-day oral treatment with bulsulfan (11 mg/kg/day). Results - Bone marrow ablation changed the elimination from non-linear to linear, consistent with an abolition of the non-linear elimination via BM EpoRs. The phlebotomy increased the linear clearance of the ablated elimination pathway (from 63.6 ± 12 to 126 ± 64 ml/h/kg), consistent with an up-regulation of the erythroid progenitor BM-based EpoR pool, but did not change the clearance of the non-ablated elimination pathway (p > 0.05). The EpoR pool size remaining after BM ablation was 7.4 ± 2.7% of the pre-ablation pool. Conclusions - Erythropoietin elimination via EpoR in the bone marrow was non-linear and increased following phlebotomy-induced anemia. This is consistent with an up-regulation of the erythropoietic EpoR pool in BM. Assuming that the elimination of Epo after BM ablation was via non-hematopoietic EpoR, then this post-ablation EpoR population was not significantly up-regulated by the phlebotomy.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalBiopharmaceutics and Drug Disposition
Volume25
Issue number4
DOIs
StatePublished - May 1 2004

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Erythropoietin Receptors
Phlebotomy
Anemia
Pharmacokinetics
Bone Marrow
Population
Erythropoietin
Up-Regulation
Cell Surface Receptors
Sheep
Stem Cells

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

Veng-Pedersen, P. ; Chapel, S. ; Al-Huniti, N. H. ; Schimdt, R. L. ; Sedars, E. M. ; Hohl, R. J. ; Widness, J. A. / Pharmacokinetic tracer kinetics analysis of changes in erythropoietin receptor population in phylebotomy-induced anemia and bone marrow ablation. In: Biopharmaceutics and Drug Disposition. 2004 ; Vol. 25, No. 4. pp. 149-156.
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title = "Pharmacokinetic tracer kinetics analysis of changes in erythropoietin receptor population in phylebotomy-induced anemia and bone marrow ablation",
abstract = "Objectives - The objective was to study in vivo erythropoietin (Epo) progenitor cell surface receptors (EpoR) in the bone marrow (BM) after phlebotomy and bone marrow ablation. Methods - Serial tracer interaction method experiments were conducted in adult sheep at baseline and after phlebotomy (PH) and ablation (AB). PH was done 10 days after phlebotomy (to 3-4g/dl Hb), and the AB was done 8 days after a 3-day oral treatment with bulsulfan (11 mg/kg/day). Results - Bone marrow ablation changed the elimination from non-linear to linear, consistent with an abolition of the non-linear elimination via BM EpoRs. The phlebotomy increased the linear clearance of the ablated elimination pathway (from 63.6 ± 12 to 126 ± 64 ml/h/kg), consistent with an up-regulation of the erythroid progenitor BM-based EpoR pool, but did not change the clearance of the non-ablated elimination pathway (p > 0.05). The EpoR pool size remaining after BM ablation was 7.4 ± 2.7{\%} of the pre-ablation pool. Conclusions - Erythropoietin elimination via EpoR in the bone marrow was non-linear and increased following phlebotomy-induced anemia. This is consistent with an up-regulation of the erythropoietic EpoR pool in BM. Assuming that the elimination of Epo after BM ablation was via non-hematopoietic EpoR, then this post-ablation EpoR population was not significantly up-regulated by the phlebotomy.",
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Pharmacokinetic tracer kinetics analysis of changes in erythropoietin receptor population in phylebotomy-induced anemia and bone marrow ablation. / Veng-Pedersen, P.; Chapel, S.; Al-Huniti, N. H.; Schimdt, R. L.; Sedars, E. M.; Hohl, R. J.; Widness, J. A.

In: Biopharmaceutics and Drug Disposition, Vol. 25, No. 4, 01.05.2004, p. 149-156.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pharmacokinetic tracer kinetics analysis of changes in erythropoietin receptor population in phylebotomy-induced anemia and bone marrow ablation

AU - Veng-Pedersen, P.

AU - Chapel, S.

AU - Al-Huniti, N. H.

AU - Schimdt, R. L.

AU - Sedars, E. M.

AU - Hohl, R. J.

AU - Widness, J. A.

PY - 2004/5/1

Y1 - 2004/5/1

N2 - Objectives - The objective was to study in vivo erythropoietin (Epo) progenitor cell surface receptors (EpoR) in the bone marrow (BM) after phlebotomy and bone marrow ablation. Methods - Serial tracer interaction method experiments were conducted in adult sheep at baseline and after phlebotomy (PH) and ablation (AB). PH was done 10 days after phlebotomy (to 3-4g/dl Hb), and the AB was done 8 days after a 3-day oral treatment with bulsulfan (11 mg/kg/day). Results - Bone marrow ablation changed the elimination from non-linear to linear, consistent with an abolition of the non-linear elimination via BM EpoRs. The phlebotomy increased the linear clearance of the ablated elimination pathway (from 63.6 ± 12 to 126 ± 64 ml/h/kg), consistent with an up-regulation of the erythroid progenitor BM-based EpoR pool, but did not change the clearance of the non-ablated elimination pathway (p > 0.05). The EpoR pool size remaining after BM ablation was 7.4 ± 2.7% of the pre-ablation pool. Conclusions - Erythropoietin elimination via EpoR in the bone marrow was non-linear and increased following phlebotomy-induced anemia. This is consistent with an up-regulation of the erythropoietic EpoR pool in BM. Assuming that the elimination of Epo after BM ablation was via non-hematopoietic EpoR, then this post-ablation EpoR population was not significantly up-regulated by the phlebotomy.

AB - Objectives - The objective was to study in vivo erythropoietin (Epo) progenitor cell surface receptors (EpoR) in the bone marrow (BM) after phlebotomy and bone marrow ablation. Methods - Serial tracer interaction method experiments were conducted in adult sheep at baseline and after phlebotomy (PH) and ablation (AB). PH was done 10 days after phlebotomy (to 3-4g/dl Hb), and the AB was done 8 days after a 3-day oral treatment with bulsulfan (11 mg/kg/day). Results - Bone marrow ablation changed the elimination from non-linear to linear, consistent with an abolition of the non-linear elimination via BM EpoRs. The phlebotomy increased the linear clearance of the ablated elimination pathway (from 63.6 ± 12 to 126 ± 64 ml/h/kg), consistent with an up-regulation of the erythroid progenitor BM-based EpoR pool, but did not change the clearance of the non-ablated elimination pathway (p > 0.05). The EpoR pool size remaining after BM ablation was 7.4 ± 2.7% of the pre-ablation pool. Conclusions - Erythropoietin elimination via EpoR in the bone marrow was non-linear and increased following phlebotomy-induced anemia. This is consistent with an up-regulation of the erythropoietic EpoR pool in BM. Assuming that the elimination of Epo after BM ablation was via non-hematopoietic EpoR, then this post-ablation EpoR population was not significantly up-regulated by the phlebotomy.

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U2 - 10.1002/bdd.395

DO - 10.1002/bdd.395

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