Document Detail


Increased erythropoietin elimination in fetal sheep following chronic phlebotomy.
MedLine Citation:
PMID:  17457660     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To determine by pharmacokinetic (PK) means the role of erythropoietin-receptor (EPO-R) upregulation in fetuses on the elimination of erythropoietin (EPO).
MATERIALS AND METHODS: Six fetal sheep were catheterized at a gestational age of 125-127 days and phlebotomized daily for 6 days. Paired tracer PK studies using recombinant human EPO (rHuEPO) were conducted in the sheep fetuses at baseline and post-phlebotomy, 7 days later. A PK model with Michaelis-Menten elimination was simultaneously fit to the PK data at baseline and post-phlebotomy for each fetus.
RESULTS: Daily phlebotomies reduced the hemoglobin levels from baseline values of 10.8 (5%) (mean (C.V.)) g/dl to a nadir of 4.5 (17%) g/dl post-phlebotomy. The endogenous EPO concentration rapidly increased after the first phlebotomy and remained elevated, although variable, thereafter. The Michaelis-Menten maximal rHuEPO elimination rate parameter, V(max), was significantly greater post-phlebotomy than at baseline (p < 0.05), increasing 1.31 fold. The fetal baseline "linear" clearance at very low concentrations of rHuEPO was determined to be 117 ml/kg/h, similar to that determined in newborn sheep but 2-3 fold higher than that determined in adult sheep.
CONCLUSIONS: The observed increase in V(max) is consistent with an up-regulation of EPO-R due to a positive feedback resulting from the phlebotomy-induced anemia.
Authors:
Kevin J Freise; John A Widness; Jeffrey L Segar; Robert L Schmidt; Peter Veng-Pedersen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-04-25
Journal Detail:
Title:  Pharmaceutical research     Volume:  24     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-02     Completed Date:  2007-09-25     Revised Date:  2010-12-03    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1653-9     Citation Subset:  IM    
Affiliation:
College of Pharmacy, The University of Iowa, 115 S. Grand Ave, Iowa City, Iowa 52242, USA.
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MeSH Terms
Descriptor/Qualifier:
Anemia / metabolism
Animals
Animals, Newborn
Erythropoietin / pharmacokinetics*
Female
Fetus / metabolism*
Phlebotomy*
Pregnancy
Receptors, Erythropoietin / physiology
Sheep
Grant Support
ID/Acronym/Agency:
P01 HL046925-12/HL/NHLBI NIH HHS; P01 HL49625/HL/NHLBI NIH HHS; R01 HL-64770/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Erythropoietin; 11096-26-7/Erythropoietin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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