New thinking in ADME-TOX boosts early confidence

Recent guidelines from regulators in the USA and Europe are very clear about the data they want to see relating to a new drug candidate's mode of action, pharmacokinetics, and interaction with biosynthetic pathways in test species and humans, as well as the levels and clinical impact of important metabolites.

In response, leading pharma and biopharma companies are adopting strategies to generate this understanding as early as is practical. As a result, in vitro ADME-TOX (absorption, distribution, metabolism, excretion, toxicity) and in vivo DMPK (drug metabolism and pharmacokinetics) studies are no longer seen as late-stage regulatory requirements, but instead an essential part of early discovery.

In addition to the regulatory drivers, the potential advantages of integrating ADME-TOX early are significant. Almost 25% of failures in Phase II and Phase III clinical trials are due to safety issues so, for researchers to develop a deeper understanding of a compound early can save millions of dollars and years of development effort that can be focussed in more viable drug candidates.

A significant toolbox of techniques is available to pharmaceutical scientists, with Mass spectrometry (MS) traditionally dominating the analytical landscape in ADME-TOX and metabolic identification (MetID). MS continues to be a core method for the detection and quantitation of metabolites. NMR can also be used to provide vital structural characterisation rather than just accurate mass data. The early combination of MS and NMR is a powerful approach that can prevent difficulties in late stage development and in the clinic.

In parallel to traditional ADME-TOX approaches, Bruker is also pioneering novel MALDI Imaging systems: visualizing and measuring drugs and metabolites directly in tissues, a breakthrough that is opening up a whole new level of histopharmacology to drug discovery and development.

Highly developed Bruker systems provide the tools needed for this new approach to early stage ADME-TOX. Find out more about: EVOQ Triple Quad MS instruments, Advance NMR platform, and rapifleX MALDI Tissuetyper.