Application of metabonomics in drug development.
Metabolic profiling (metabonomics/metabolomics) is the untargeted analysis of metabolic composition in a biological sample, and is principally aimed at biomarker discovery. The frequent use of noninvasive biofluid analysis in metabonomics is suited to the clinic and facilitates dynamic monitoring. Analytical protocols for metabolic biomarkers are potentially robust because a metabolite is the same chemical entity irrespective of its origin, facilitating 'bench-to-bedside' translational research. Metabonomics can make an impact at several points in the drug-development process: target identification; lead discovery and optimization; preclinical efficacy and safety assessment; mode-of-action and mechanistic toxicology; patient stratification; and clinical pharmacological monitoring. This review describes and exemplifies the latest developments in each of these areas, including the impact of new data and chemical analytical techniques. The future goals for metabonomics are the validation of existing biomarkers, in terms of mechanism and translation to man, together with a focus on characterizing the individual ('personalized healthcare').
Keun
Hector C
HC
Imperial College London, Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics (SORA), Faculty of Medicine, South Kensington, London, SW7 2AZ, UK. h.keun@imperial.ac.uk
Athersuch
Toby J
TJ
D004358:Drug Therapy / Q000379:methods; D020869:Gene Expression Profiling; D006801:Humans; D008660:Metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism* / Q000592:standards; D012449:Safety
D004364:Pharmaceutical Preparations