Oral administration of peptide-based drugs: Beyond Lipinski's rule

Gabriela B. Santos, A. Ganesan, Flavio S. Emery

Research output: Contribution to journalLiterature review

99 Citations (Scopus)


The use of peptides in therapy presents several limitations, from physicochemical characteristics to inadequate pharmacokinetic profiles for oral absorption. As peptides are gaining importance in the therapeutic arsenal, there is an increasing need to rationalize the main characteristics of this compound class in the market. Therefore, we performed an extensive analysis of all known peptide drugs and clinical candidates based on their peptide features, physicochemical and structural properties, and correlated these with their administration route and therapeutic classes. Peptide drugs are widely distributed across drug and pharmacological space, covering several therapeutic areas with structural diversity and complexity, distributed between groups of cyclic and linear compounds. Although structural and physicochemical properties are clear within these groups, we counter the consensus that cyclic peptides have better oral availability than linear peptides, as most of the orally administrated peptides have linear structures. This study and review furnishes information that could support peptide drug design, with a new cutoff of known descriptors that go beyond the Rule of Five.
Original languageEnglish
Pages (from-to)2245–2251
Number of pages7
Issue number20
Early online date6 Sep 2016
Publication statusPublished - 19 Oct 2016


  • drug discovery
  • drug likeness descriptors
  • drugs
  • peptides
  • physicochemical properties

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