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Research ArticleSpecial Section on DMPK of Therapeutic Proteins—Minireview

Absorption, Distribution, Metabolism, and Excretion Considerations for the Development of Antibody-Drug Conjugates

Tae H. Han and Baiteng Zhao
Drug Metabolism and Disposition November 2014, 42 (11) 1914-1920; DOI: https://doi.org/10.1124/dmd.114.058586
Tae H. Han
Stem CentRx, Inc. (T.H.H.), South San Francisco, California; Seattle Genetics, Inc. (B.Z.), Bothell, Washington
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Baiteng Zhao
Stem CentRx, Inc. (T.H.H.), South San Francisco, California; Seattle Genetics, Inc. (B.Z.), Bothell, Washington
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Abstract

Antibody-drug conjugates (ADCs) are a class of therapeutics that are designed to deliver potent small-molecule drugs selectively to cells that express a specific target antigen while limiting systemic exposure to the drug. This is accomplished by conjugating a potent drug onto an antibody-based therapeutic with a linker that is exquisitely stable in plasma. The development of an effective ADC requires optimizing a number of design elements and an extensive understanding of absorption, distribution, metabolism/catabolism, and elimination (ADME) processes for the ADC construct. Furthermore, as ADCs are a combination of an antibody and small-molecule drug, understanding key aspects of the ADME of each individual component is needed. This review aims to provide considerations for the development of ADCs from an ADME point of view.

Footnotes

    • Received April 12, 2014.
    • Accepted July 21, 2014.
  • dx.doi.org/10.1124/dmd.114.058586.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 42 (11)
Drug Metabolism and Disposition
Vol. 42, Issue 11
1 Nov 2014
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Research ArticleSpecial Section on DMPK of Therapeutic Proteins—Minireview

ADME Considerations for Antibody-Drug Conjugates

Tae H. Han and Baiteng Zhao
Drug Metabolism and Disposition November 1, 2014, 42 (11) 1914-1920; DOI: https://doi.org/10.1124/dmd.114.058586

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Research ArticleSpecial Section on DMPK of Therapeutic Proteins—Minireview

ADME Considerations for Antibody-Drug Conjugates

Tae H. Han and Baiteng Zhao
Drug Metabolism and Disposition November 1, 2014, 42 (11) 1914-1920; DOI: https://doi.org/10.1124/dmd.114.058586
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  • Article
    • Abstract
    • Introduction
    • Antibody-Drug Conjugate Stability
    • Biodistribution
    • Catabolism/Metabolism
    • Elimination
    • Bioanalytical Considerations
    • Clinical Pharmacokinetics
    • Conclusion
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  • SC Absorption of Biotherapeutics
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