Document Detail


A comparison of nonlinear pharmacokinetics of erythropoietin in sheep and humans.
MedLine Citation:
PMID:  10440797     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The primary mechanism of erythropoietin's (EPO) in vivo elimination and the tissue, or tissues, responsible are unknown. Previous studies indicating that EPO pharmacokinetic (PK) behaviour is nonlinear suggest that EPO elimination takes place by a saturable mechanism. A versatile PK system analysis, the Disposition Decomposition Analysis (DDA), capable of quantification of the Michaelis-Menten parameters, V(m) and k(m) was used to analyze and compare EPO's PK behaviour in newborn sheep and preterm infants. Lambs and infants both demonstrated nonlinear PK behaviour appropriately analyzed with DDA. Compared to preterm infants, lambs had significantly greater (p<0.05) elimination capacity as determined by the V(m) (2789+/-525 versus 1767+/-250 mU/mL per h (mean+/-S.E.), respectively), and larger extrapolated linear clearances (116+/-19.1 versus 21.3+/-1.75 mL/kg per h, respectively) (p<0.01). Lambs also demonstrated significantly larger (p<0.01) degrees of nonlinearity as judged by smaller mean k(m) values (2142+/-258 versus 6796+/-1.007 mU/mL, respectively). Of note, although the DDA does not distinguish what the mechanism of EPO elimination is, enzymatic degradation and receptor-mediated cellular internalization are two possibilities. The in vivo DDA-derived k(m) values were similar to reported in vitro binding affinity k(d) data for erythroid progenitors and cell lines having EPO-R's, i.e. 240-2400 mU/mL. The present study's demonstration that EPO's nonlinear PK behaviour in both sheep and humans can be analyzed by the DDA methodology indicates that the sheep model may be used in invasive studies needed to further characterize the mechanism of EPO elimination.
Authors:
P Veng-Pedersen; J A Widness; L M Pereira; R L Schmidt; L S Lowe
Related Documents :
8130867 - Methylene blue-induced heinz body hemolytic anemia.
6543847 - The use of sweat osmolality in the diagnosis of cystic fibrosis.
6416017 - Intra-uterine transfusions to the rhesus-immunized fetus in the department of obstetric...
362367 - Microangiopathic hemolytic anemia and thrombocytopenia in a neonate associated with a l...
8890077 - Serial changes in titers of antibody to hepatitis b surface antigen after immunization ...
15130527 - Patterns of brain electrical activity in infants of depressed mothers who breastfeed an...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biopharmaceutics & drug disposition     Volume:  20     ISSN:  0142-2782     ISO Abbreviation:  Biopharm Drug Dispos     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-09-17     Completed Date:  1999-09-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7911226     Medline TA:  Biopharm Drug Dispos     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  217-23     Citation Subset:  IM    
Copyright Information:
Copyright 1999 John Wiley & Sons, Ltd.
Affiliation:
College of Pharmacy, Division of Pharmaceutics, University of Iowa, Iowa City, IA 52242, USA. veng@uiowa-edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn / metabolism*
Erythropoietin / blood,  pharmacokinetics*
Female
Gestational Age
Humans
Infant, Newborn
Infant, Premature / metabolism*
Male
Sheep
Species Specificity
Grant Support
ID/Acronym/Agency:
GCRC RR00059/RR/NCRR NIH HHS; P01 HL46925/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
11096-26-7/Erythropoietin

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


Previous Document:  Renal excretion mechanism of NS-49, a phenethylamine class alpha 1A-adrenoceptor agonist.
Next Document:  Gender differences in pharmacokinetics and pharmacodynamics of azosemide in rats.