Voltammetric Behaviour of Drug Molecules as a Predictor of Metabolic Liabilities

Hikari Fuchigami, Mandeep K. Bal, Dale A. C. Brownson, Craig E. Banks, Alan M. Jones

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Electron transfer plays a vital role in drug metabolism and underlying toxicity mechanisms. Currently, pharmaceutical research relies on pharmacokinetics (PK) and absorption, distribution, metabolism, elimination and toxicity (ADMET) measurements to understand and predict drug reactions in the body. Metabolic stability (and toxicity) prediction in the early phases of the drug discovery and development process is key in identifying a suitable lead compound for optimisation. Voltammetric methods have the potential to overcome the significant barrier of new drug failure rates, by giving insight into phase I metabolism events which can have a direct bearing on the stability and toxicity of the parent drug being dosed. Herein, we report for the first time a data-mining investigation into the voltammetric behaviour of reported drug molecules and their correlation with metabolic stability (indirectly measured via t 1/2), as a potential predictor of drug stability/toxicity in vivo. We observed an inverse relationship between oxidation potential and drug stability. Furthermore, we selected and prepared short-(<10 min) and longer-circulation (>2 h) drug molecules to prospectively survey the relationship between oxidation potential and stability.

Original languageEnglish
Article number46
Pages (from-to)1-15
Number of pages15
JournalScientia Pharmaceutica
Volume88
Issue number4
DOIs
Publication statusPublished - 13 Oct 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Drug
  • Drug discovery
  • Electron transfer
  • Half-life
  • Metabolism
  • Propanidid
  • Stability
  • Toxicity
  • Voltammetry

ASJC Scopus subject areas

  • Pharmaceutical Science

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