Metabonomic modeling of drug toxicity

Global metabolic profiling (metabonomics/metabolomics) has shown particular promise in the area of toxicology and drug development. In both preclinical screening and mechanistic exploration, metabolic profiling can offer rapid, noninvasive toxicological information that is robust and reproducible, with little or no added technical resources to existing studies in drug metabolism and toxicity. In this review, the study design and analytical technology required for metabonomics are discussed, along with key examples of how fundamental questions in drug development can be addressed. Strategies for metabonomic data analysis in toxicity assessment are detailed in both principle and practice, together with a description of toxicologically relevant metabolic biomarkers. Extended into the assessment of efficacy and toxicity in the clinic, metabonomics may prove crucial in making personalized therapy and pharmacogenomics a reality. (c) 2005 Elsevier Inc. All rights reserved.