The role of metabonomics at the interface between drug metabolism and safety assessment.
Safety assessment of candidate drugs is a key stage in drug development and one which represents a significant attritional hurdle. There is also a focused effort in drug metabolism studies to assess bioactivation potential based on the notion this could lead to the risk of macromolecule adduct formation and subsequent toxicological consequences. However, characterization of the molecular mechanisms of drug toxicity still remains an enormous challenge. Recent advancements in 'omics sciences, and in particular metabonomics, has enabled some elucidation or insights into toxicological sequelae. Metabonomics is a global metabolic profiling framework which utilizes high resolution analytics (typically NMR and mass spectrometry) together with chemometric statistical tools (such as principal component analysis and partial least squares) to derive an integrated picture of both endogenous and xenobiotic metabolism. This review details some of the current progress in the application of metabonomics in drug safety and metabolism.
Waters
Nigel J
NJ
Metabolism & Pharmacokinetics, Novartis Institutes for Biomedical Research, 250 Massachusetts Ave, Cambridge, MA 02139, USA. nigel.waters@novartis.com
D000818:Animals; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D025341:Principal Component Analysis; D015262:Xenobiotics / Q000009:adverse effects / Q000378:metabolism
D004364:Pharmaceutical Preparations; D015262:Xenobiotics