Longitudinal pharmacometabonomics for predicting patient responses to therapy: drug metabolism, toxicity and efficacy

Abstract

Pharmacometabonomics describes the use of metabolic profiling of biofluids, tissues and tissue extracts to predict, prior to dosing, the beneficial and adverse effects of an intervention such as drug administration. The approach not only is analogous to pharmacogenomics but also is sensitive to environmental factors such as the gut microbiome. Recent applications of pharmacometabonomics are presented and the extension to the use of longitudinal sampling is introduced. Clinical and other human applications of pharmacometabonomics are highlighted and possible future clinical applications of pharmacometabonomics and longitudinal pharmacometabonomics are discussed. These include clinical trials of new drugs either at the first-into-man stage or later in Phase II and III trials, and assessment of individual patients or groups of patients for particular therapies (personalised and stratified medicine approaches). Since metabonomics approaches are sensitive to both the host genome effects and the gut microbiome, pharmacometabonomics has particular utility for studying the host–microbiome interactions and for assessing new therapies that target the gut bacteria. Since the microbiome also has implications for nutrition and drug pharmacokinetics, such metabolic profiling approaches are likely to of use in such studies. It is anticipated that as metabonomics analytical and statistical technologies continue to develop, more applications will be realised and these should find use in real clinical situations, even monitoring patients in real time.

Keywords:

• chemotherapy
• diagnosis
• drug metabolism
• genomics
• metabolomics
• metabonomics
• personalised health care
• pharmacogenomics
• pharmacometabonomics
• prognosis
• surgery
• toxicity