Traditional drug metabolism studies of animals use species-matched subjects to gain insight into metabolic outcomes through in vivo drug administrations. Although unrivalled in terms of reflecting biological processes, there are notable complications to this approach. Firstly, ethical issues concerning the use of animals and humans in drug trials can hamper experiments and prevent full exploration of scientific hypotheses. Ethical clearance is further challenged when the substance to be administered is a novel drug, as there are limited or no toxicological data to support its safe use. The use of new psychoactive substances (NPS) continues to grow in the community, as evidenced by wastewater detections, and understanding such substances has become more crucial.1 Operational costs are not trivial for in vivo administration studies. These studies require provisions to be made to the numerous participants (e.g. food, water, shelter) with specialist labour costs (e.g. veterinarian) over a prolonged period of time (days to weeks).
Since the conceptualisation of metabolism models in the nineteenth century, anti-doping laboratories globally have continued to use models to quickly address emerging drug threats, prior to conducting the more cumbersome in vivo drug administrations. Reported here are insights obtained from the practical application of the various metabolism models at Racing Analytical Services Limited. These models include liver preparations, electrochemistry, in silico prediction tools (Biotransformer) and zebrafish. A key significance of metabolism models is their applicability in reporting drug detections relevant to the animal racing industry. ILAC-G7, a document providing guidelines for drug identification in horseracing laboratories, specifies that an in vitro platform (metabolism model) may be used.2 If the platform can demonstrate that its reaction products are drug metabolites detected in the incurred sample, the comparison data can be used as evidence of drug administration. This makes investment in the metabolism models a worthwhile venture for drug control.