The AAPS Journal

, Volume 17, Issue 1, pp 134–143 | Cite as

Strategic Approaches to Optimizing Peptide ADME Properties

Review Article Theme: Preclinical Peptide Developability Assessment
Part of the following topical collections:
  1. Theme: Preclinical Peptide Developability Assessment

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.

KEY WORDS

ADME peptides pharmacokinetics proteolysis renal clearance 

Notes

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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Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  1. 1.Pharmacokinetics, Dynamics and MetabolismPfizer Inc.GrotonUSA

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