Antibodies as carrier proteins

Pre-existing antibodies against a drug substance can significantly alter the pharmacokinetic profile of the drug in the circulation. Rapid clearance, mediated by complement or Fc receptors, occurs for crosslinked immune complexes, but not for complexes containing only one or two antibodies. With ant...

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Bibliographic Details
Published in:Pharmaceutical research 1998-11, Vol.15 (11), p.1652-1656
Main Authors: REHLAENDER, B. N, CHO, M. J
Format: Article
Language:English
Subjects:
Antidotes
Antigen-Antibody Reactions
Biological and medical sciences
Carrier Proteins - metabolism
Cytokines - immunology
Cytokines - pharmacokinetics
General pharmacology
Humans
Insulin - immunology
Insulin - pharmacokinetics
Medical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacokinetics
Pharmacology. Drug treatments
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Summary:Pre-existing antibodies against a drug substance can significantly alter the pharmacokinetic profile of the drug in the circulation. Rapid clearance, mediated by complement or Fc receptors, occurs for crosslinked immune complexes, but not for complexes containing only one or two antibodies. With antibodies functioning as carrier proteins, monovalent antigens may enjoy a prolonged circulatory half-life, as observed in the case of digoxin, insulin, and various interleukins. While such an effect should be highly sensitive to fluctuations in antibody affinity and titer, it may present a means of extending the circulation of potent but rapidly cleared therapeutic agents. This mini-review attempts to delineate the causal relation between the factors influencing antibody binding and the circulatory life of a therapeutic agent, be it a small drug or a macromolecule.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1011936007457