Metabonomics in preclinical safety evaluation

ANYL 190

Donald G. Robertson, donald.robertson@pfizer.com, Safety Sciences, Pfizer Global Research and Development, 2800 Plymouth Rd, Ann Arbor, MI 48105
Within the realm of preclinical pharmaceutical evaluation, we are at a point where we can ask if the early promise of metabonomics has been realized or not. While the hope for a rapid throughput safety screen has not disappeared, the complexity of basic biochemistry stymies simplicity. The benefits of understanding this complexity may allow us to understand what we have always attributed to inter-animal or inter-study variation. This in turn may allow us to run studies with fewer animals and explain the odd responder that frequently reduces apparent safety margins. Metabonomics enables early and rapid assessment of safety related issues at a depth of biochemical analysis that was previously impractical, with mechanisms and safety biomarkers a frequent byproduct. This presentation will elaborate on the applications of metabonomics in preclinical safety assessment, what has worked and what still needs to be worked out with regard to screening, biomarkers and mechanistic toxicology.