Linked Life Data

12784166

Source:http://linkedlifedata.com/resource/pubmed/id/12784166

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-6-4
pubmed:abstractText
The aim of this study was to develop a pharmacokinetic model that takes into account the negative feedback loop of endogenous erythropoietin production observed after repeated recombinant human erythropoietin administration. A pharmacodynamic data analysis was performed using the changes in i) reticulocyte count, ii) serum levels of soluble transferrin receptors, and iii) soluble transferrin receptors/serum proteins ratio as an index of the therapeutic effect of the hormone. Nine athletes were included in the study; they received repeated subcutaneous administrations (50 IU x kg(-1) per day) of recombinant human erythropoietin. The mean half-life of the terminal part of the curve was 35.5 h, and the total clearance was 17 ml x h(-1) x kg(-1). The total clearance was about two times higher in athletes than in untrained subjects (5.5 - 7.5 ml x h(-1) x kg(-1)) and the half-life period of plasma erythropoietin after subcutaneous administration was five times longer compared to intravenous administration (4 to 7 h). Thus, after subcutaneous administration, the terminal part of the curve should correspond to the absorption phase, instead of to the elimination phase (flip-flop phenomenon). The pharmacodynamic relationship based on a sigmoid Emax model can be reasonably used to relate the changes observed in the markers to recombinant human erythropoietin administration. Recombinant human erythropoietin induces a delayed increase in reticulocytosis and in soluble transferrin receptor levels. In comparison with baseline, the increase of these markers became significant from the third and the tenth day after the initial administration of the hormone, respectively. These results were in accordance with the equilibration delay computed from the pharmacokinetic-pharmacodynamic data modelling (half-life of 25.7 h and 10 days, respectively). The recombinant hormone was well tolerated during this study.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0172-4622
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
252-7
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Pharmacokinetic-pharmacodynamic modelling of recombinant human erythropoietin in athletes.
pubmed:affiliation
Laboratoire de Pharmacocinétique Clinique, Faculté de Pharmacie, Université Montpellier I, France.
pubmed:publicationType
Journal Article, Clinical Trial