The use of equine hepatocytes for the prediction of the pharmacokinetics and potential drug-drug interactions of Meloxicam and the nutraceutical Quercetin (360G-Wellcome-206817_Z_17_Z)

There is limited information available about equine drug metabolism to ensure optimal dosing, decrease risks of drug-drug interactions and to predict the effects of treatments. New findings are particularly important in the horse racing industry and for equine welfare.  As there are ethical issues associated with in vivo experimentation, using equine hepatocytes to develop a highly predictable horse in vitro model to estimate the in vivo clearance and potential drug-drug interactions may be a way forward. This would reduce costs and reduce and refine animal testing. More research is needed to understand its benefits and limitations.  This project is designed to use fresh and cryopreserved equine hepatocytes to predict the in vivo pharmacokinetics of Meloxicam, commonly used for the treatment of inflammation. This drug will be used as its pharmacokinetic data in the horse is known. Furthermore, potential drug-drug interactions of Meloxicam with Quercetin, a flavanol, used in equine nutraceutical products as an anti-inflammatory will be assessed.  The main experimental aims are to compare metabolism (enzyme kinetics) of Meloxicam in fresh and cryopreserved equine hepatocytes and scale results physiologically to estimate hepatic clearance. These results will then be compared with measured pharmacokinetic blood clearance obtained from in vivo pharmacokinetics.