| 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.