Metabonomics in pharmaceutical R&D.
This minireview is based on a lecture given at the First Maga Circe Conference on metabolomics held at Sabaudia, Italy, in March 2006 in which the analytical and statistical techniques used in metabonomics, efforts at standardization and some of the major applications to pharmaceutical research and development are reviewed. Metabonomics involves the determination of multiple metabolites simultaneously in biofluids, tissues and tissue extracts. Applications to preclinical drug safety studies are illustrated by the Consortium for Metabonomic Toxicology, a collaboration involving several major pharmaceutical companies. This consortium was able, through the measurement of a dataset of NMR spectra of rodent urine and serum samples, to build a predictive expert system for liver and kidney toxicity. A secondary benefit was the elucidation of the endogenous biochemicals responsible for the classification. The use of metabonomics in disease diagnosis and therapy monitoring is discussed with an exemplification from coronary artery disease, and the concept of pharmaco-metabonomics as a way of predicting an individual's response to treatment is exemplified. Finally, some advantages and perceived difficulties of the metabonomics approach are summarized.
Lindon
John C
JC
Biomolecular Medicine, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College London, South Kensington, London, UK. j.lindon@imperial.ac.uk
Holmes
Elaine
E
Nicholson
Jeremy K
JK
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D005544:Forecasting; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D010597:Pharmacogenetics; D010600:Pharmacology; D013678:Technology, Pharmaceutical / Q000379:methods*
D015415:Biomarkers; D004364:Pharmaceutical Preparations