Enhanced elimination of biotinylated antibodies by avidin-based hemoperfusion in rats.
We designed a hemoperfusion system using immobilized avidin for selective removal of biotinylated therapeutic antibodies from rats. Two prototype therapeutic antibodies, ovine antidigoxin Fab fragment and murine monoclonal 8A1 against Escherichia coli J5 lipopolysaccharide endotoxin, were biotinylated using biotin-long-chain-N-hydroxysuccinimide ester. Biotinylated antibodies were administered i.v. to anesthetized rats which were instrumented for measurement of cardiovascular parameters and connected to avidin-hemoperfusion devices. By using several different protocols of antibody administration and hemoperfusion, we found that the half-lives and areas under the time vs. concentration curves of biotinylated antibodies were reduced significantly after passage over immobilized avidin. Avidin hemoperfusion was not associated with adverse changes in blood pressure, heart rate or excess hemolysis. These data suggest that avidin hemoperfusion affords a means for selective removal of biotinylated ligands from serum, and that other therapeutic and potentially toxic compounds could be removed in this manner.
Center for Emergency Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey.
K K
KK
Burkhart
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D
Beard
M L
ML
Billingsley
D000818:Animals; D000906:Antibodies / Q000097:blood* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000097:blood / Q000378:metabolism; D001360:Avidin; D001710:Biotin / Q000378:metabolism* / Q000493:pharmacokinetics; D004077:Digoxin / Q000276:immunology; D004731:Endotoxins / Q000276:immunology; D006207:Half-Life; D006464:Hemoperfusion / Q000379:methods*; D007128:Immunoglobulin Fragments / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep
D000906:Antibodies; D000911:Antibodies, Monoclonal; D004731:Endotoxins; D007128:Immunoglobulin Fragments; D001360:Avidin; C044101:endotoxin, Escherichia coli; D001710:Biotin; D004077:Digoxin