Pharmacokinetic tracer kinetics analysis of changes in erythropoietin receptor population in phlebotomy-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 3-4 g/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.

• Authors: P Veng-Pedersen, S Chapel, N H Al-Huniti, R L Schmidt, E M Sedars, R J Hohl, J A Widness
• Journal: Biopharmaceutics & drug disposition (Biopharm Drug Dispos) Vol. 25 Issue 4 Pg. 149-56 (May 2004) ISSN: 0142-2782 [Print] England
• PMID: 15108217 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2004 John Wiley & Sons, Ltd.

Chemical References

• Alkylating Agents
• Receptors, Erythropoietin
• Recombinant Proteins
• Erythropoietin
• Busulfan

Topics

• Alkylating Agents (pharmacology)
• Anemia (etiology, metabolism)
• Animals
• Bone Marrow (drug effects, metabolism)
• Busulfan (pharmacology)
• Catheter Ablation
• Erythropoietin (blood, pharmacokinetics)
• Half-Life
• Metabolic Clearance Rate
• Phlebotomy
• Receptors, Erythropoietin (metabolism)
• Recombinant Proteins
• Sheep