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Oral drug suitability parameters.

MedChemCommยท2018
See all related articles
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Related Experiment Video

Updated: Feb 6, 2026

Use of Micropipette-Guided Drug Administration as an Alternative Method to Oral Gavage in Rodent Models
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Designing safer oral drugs.

M C Wenlock1

  • 1InSilicoLynx Ltd , BioHub at Alderley Park , Mereside, Alderley Park , Cheshire , SK10 4TG , UK .

Medchemcomm
|August 16, 2018
PubMed
Summary

A new criterion for oral drug design suggests limiting the amount of drug in the body at steady state to 0.5 mg/kg. This approach aims to improve drug efficacy and reduce toxicity in humans.

Area of Science:

  • Pharmacology
  • Drug Discovery
  • Toxicology

Background:

  • Designing safe and effective oral drugs is challenging, especially with limited early-stage safety data.
  • Current methods rely on physicochemical properties and log P for guidance, but these have limitations.
  • Understanding the relationship between drug properties and human toxicity is crucial for drug development.

Purpose of the Study:

  • To propose an alternative heuristic criterion for designing efficacious oral drugs with reduced toxicity.
  • To establish a threshold for the amount of compound in the body at steady state in humans.
  • To provide a method for assessing a compound's estimated in vivo plasma levels against a therapeutic window.

Main Methods:

  • A novel criterion based on the amount of compound in the body at steady state was developed.

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  • This criterion was established using minimum toxic blood-plasma concentration data from 242 oral drugs.
  • The proposed threshold for humans is 0.5 mg/kg.
  • Main Results:

    • A steady-state amount of 0.5 mg/kg is proposed as a human threshold for oral drug design.
    • This criterion can be used to estimate a therapeutic window for new drug candidates.
    • The study discusses the relationship between this criterion, oral dose sizes, charge types, and in vivo plasma clearances.

    Conclusions:

    • The proposed steady-state amount criterion offers a new heuristic for designing safer and more effective oral drugs.
    • This approach can aid in early-stage drug design by predicting potential toxicity liabilities.
    • Further assessment of estimated in vivo plasma levels against this threshold can guide dose selection and optimization.