Enhanced elimination of biotinylated antibodies by avidin-based hemoperfusion in rats

K. K. Burkhart, D. Beard, M. L. Billingsley

    Research output: Contribution to journalArticlepeer-review

    3 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)356-361
    Number of pages6
    JournalJournal of Pharmacology and Experimental Therapeutics
    Volume270
    Issue number1
    StatePublished - Jan 1 1994

    All Science Journal Classification (ASJC) codes

    • Molecular Medicine
    • Pharmacology

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