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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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The application of metabonomics to predict drug-induced liver injury

T M O'Connell1, P B Watkins

  • 1Hamner-UNC Institute for Drug Safety Sciences, Research Triangle Park, North Carolina, USA. tom_oconnell@med.unc.edu

Clinical Pharmacology and Therapeutics
|July 30, 2010
PubMed

Insights

Metabonomics, the study of metabolic profiles, shows promise for early detection of drug-induced liver injury (DILI). Analyzing metabolites in biofluids can identify patients at risk before symptoms appear.

Area of Science:

  • Biochemistry
  • Toxicology
  • Analytical Chemistry

Background:

  • Drug-induced liver injury (DILI) is a significant patient safety concern and a frequent reason for regulatory actions.
  • Current methods for early DILI detection and prediction are insufficient.
  • Alterations in the metabolome (endogenous metabolite profiles) may precede overt DILI.

Purpose of the Study:

  • To review the emerging role of metabonomics in predicting and understanding DILI mechanisms.
  • To highlight the potential of metabonomics for early DILI detection in clinical trials.

Main Methods:

  • Metabonomics utilizes analytical technologies like nuclear magnetic resonance (NMR) and mass spectrometry (MS).
  • Analysis of endogenous metabolite profiles in biofluids (plasma, urine).

Main Results:

  • Human clinical trials demonstrated that metabonomics can identify patients likely to develop DILI.
  • Acetaminophen (APAP) and ximelagatran trials showed predictive metabonomic signatures.
  • Pre- and post-dosing biofluid analysis identified individuals at risk for DILI.

Conclusions:

  • Metabonomics offers a promising approach for the early prediction and mechanistic understanding of DILI.
  • Integrating metabonomic investigations into clinical trials of hepatotoxic drugs is recommended.
  • This approach can enhance patient safety and inform regulatory decisions.

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