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Strategic Approaches to Optimizing Peptide ADME Properties

  • Review Article
  • Theme: Preclinical Peptide Developability Assessment
  • Published:
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Abstract

Development of peptide drugs is challenging but also quite rewarding. Five blockbuster peptide drugs are currently on the market, and six new peptides received first marketing approval as new molecular entities in 2012. Although peptides only represent 2% of the drug market, the market is growing twice as quickly and might soon occupy a larger niche. Natural peptides typically have poor absorption, distribution, metabolism, and excretion (ADME) properties with rapid clearance, short half-life, low permeability, and sometimes low solubility. Strategies have been developed to improve peptide drugability through enhancing permeability, reducing proteolysis and renal clearance, and prolonging half-life. In vivo, in vitro, and in silico tools are available to evaluate ADME properties of peptides, and structural modification strategies are in place to improve peptide developability.

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Acknowledgments

The author would like to thank Karen Atkinson for editing the manuscript; Angela Doran, Angela Wolford, and Amit Kalgutkar for the study on peptide PK prediction; and Larry Tremaine, Tess Wilson, and Charlotte Allerton for their leadership and support.

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  1. Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Groton, Connecticut, 06340, USA

    Li Di

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Correspondence to Li Di.

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Guest Editors: Annette Bak and Weiguo Dai

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Di, L. Strategic Approaches to Optimizing Peptide ADME Properties. AAPS J 17, 134–143 (2015). https://doi.org/10.1208/s12248-014-9687-3

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  • DOI: https://doi.org/10.1208/s12248-014-9687-3

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