Linked Life Data

12783109

Source:http://linkedlifedata.com/resource/pubmed/id/12783109

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-6-3
pubmed:abstractText
Recombinant hirudin (r-hirudin) is a potent direct thrombin inhibitor with immunogenic properties. Anti-hirudin antibodies (aHAb) are detected in up to 74% of patients treated with r-hirudin for more than 5 days. aHAb may alter the pharmacokinetics and pharmacodynamics of r-hirudin. The effects of aHAb on the pharmacokinetics of r-hirudin were investigated in rats receiving r-hirudin intravenously either without aHAb (controls), 15 min after intravenous administration of non-specific antibodies or aHAb, and after pre-incubation with aHAb. When both were compared to controls and pre-treatment with non-specific antibodies, aHAb significantly altered the pharmacokinetics of r-hirudin with similar effects in both approaches: In the presence of aHAb, the volume of distribution in a steady state and total plasma clearance were diminished, while the half-life of elimination was prolonged. Both the maximum r-hirudin plasma concentration and the area under the curve were increased. In addition, r-hirudin filtration by high-flux hemodialyzer membranes (polysulfone, AN69) was investigated 1) in the absence of aHAb, 2) in the presence of non-specific mouse antibodies, and 3) in the presence of three monoclonal aHAb. In the absence of aHAb, both hemodialyzers allowed for significant r-hirudin filtration. Non-specific mouse antibodies did not markedly affect r-hirudin filtration. By contrast, all three aHAb almost completely hindered r-hirudin filtration. aHAb varied in their capacity to neutralize r-hirudin. In conclusion, aHAb markedly alter the pharmacokinetics of r-hirudin leading to r-hirudin accumulation. In the presence of aHAb, hemofiltration does not allow for rapid reduction of r-hirudin concentration. aHAb are capable of modifying pharmacodynamics of r-hirudin. Close monitoring of aHAb-positive patients treated with r-hirudin is considered mandatory.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
973-82
pubmed:dateRevised
2006-4-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Anti-hirudin antibodies alter pharmacokinetics and pharmacodynamics of recombinant hirudin.
pubmed:affiliation
University Hospital Freiburg, Department of Medicine, Division of Nephrology and General Medicine, Hugstetter Str. 55, D-79106 Freiburg, Germany. fischer@med1.ukl.uni-freiburg.de
pubmed:publicationType
Journal Article