| 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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Chemogenomic analysis identifies geldanamycins as substrates and inhibitors of ABCB1.
Next Document: Transdermal delivery of cytochrome C--A 12.4 kDa protein--across intact skin by constant-current ion...